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Gastrulation and Neurulation

Both gastrulation and neurulation are critical events that occur during the 3rd week of embryonic development. Gastrulation is the process by which the bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development differentiates into a trilaminar disc, made up of the 3 primary germ layers: the ectoderm, mesoderm, and endoderm. During this process, a structure called the notochord is formed in the midline in the mesodermal layer; the notochord is critical in inducing neurulation. Neurulation is the process by which some of the ectoderm in the trilaminar embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week develops into the neural tube and neural crest Neural crest The two longitudinal ridges along the primitive streak appearing near the end of gastrulation during development of nervous system (neurulation). The ridges are formed by folding of neural plate. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the neural tube. Hirschsprung Disease cells, which will go on to form all of the neural tissue in the body. This process is completed by the end of the 3rd week.

Last updated: Sep 1, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Review of Early Development

Morula Morula An early embryo that is a compact mass of about 16 blastomeres. It resembles a cluster of mulberries with two types of cells, outer cells and inner cells. Morula is the stage before blastula in non-mammalian animals or a blastocyst in mammals. Fertilization and First Week, blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week, and bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development

  • Zygote Zygote The fertilized ovum resulting from the fusion of a male and a female gamete. Fertilization and First Week: diploid Diploid The chromosomal constitution of cells, in which each type of chromosome is represented twice. Symbol: 2n or 2x. Basic Terms of Genetics cell resulting from the fusion of 2 haploid Haploid The chromosomal constitution of cells, in which each type of chromosome is represented once. Symbol: n. Basic Terms of Genetics gametes
  • Blastomeres: individual cells at the 2-, 4-, and 8-cell stages
  • Morula Morula An early embryo that is a compact mass of about 16 blastomeres. It resembles a cluster of mulberries with two types of cells, outer cells and inner cells. Morula is the stage before blastula in non-mammalian animals or a blastocyst in mammals. Fertilization and First Week: “ball of cells” starting at the 16-cell stage
  • Blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week:
    • Morula Morula An early embryo that is a compact mass of about 16 blastomeres. It resembles a cluster of mulberries with two types of cells, outer cells and inner cells. Morula is the stage before blastula in non-mammalian animals or a blastocyst in mammals. Fertilization and First Week develops a cavity called a blastocele.
    • “Positional signals” (i.e., signals released from different cells based on their position in the blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week) trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation cells to differentiate into: 
      • Outer cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast: outer shell of cells
      • Inner cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast: a clump of cells inside the shell next to the blastocele
  • Zona pellucida Zona pellucida A tough transparent membrane surrounding the ovum. It is penetrated by the sperm during fertilization. Fertilization and First Week
    • A layer of extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars surrounding embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week through the blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week stage
    • Prevents embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week from implanting in the fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy (where fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week typically occurs)
  • Outer cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast trophoblast Trophoblast Cells lining the outside of the blastocyst. After binding to the endometrium, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (placenta). Fertilization and First Week ( cytotrophoblast Cytotrophoblast Embryoblast and Trophoblast Development and syncytiotrophoblast Syncytiotrophoblast Embryoblast and Trophoblast Development) → placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity and membranes
  • Inner cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast embryoblast Embryoblast Embryoblast and Trophoblast Development bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development:
  • Amniotic sac: a cavity of fluid that develops “above” the epiblast Epiblast Embryoblast and Trophoblast Development (between epiblast Epiblast Embryoblast and Trophoblast Development and cytotrophoblast Cytotrophoblast Embryoblast and Trophoblast Development)
  • Primary yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development: a cavity that forms “below” the hypoblast Hypoblast Embryoblast and Trophoblast Development (between hypoblast Hypoblast Embryoblast and Trophoblast Development and cytotrophoblast Cytotrophoblast Embryoblast and Trophoblast Development)

Implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week

  • Occurs around days 7–9 after fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week
  • Cytotrophoblast Cytotrophoblast Embryoblast and Trophoblast Development: outer layer of cells of blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week
  • Syncytiotrophoblast Syncytiotrophoblast Embryoblast and Trophoblast Development
    • Trophoblast Trophoblast Cells lining the outside of the blastocyst. After binding to the endometrium, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (placenta). Fertilization and First Week cells in contact with uterine wall that have lost their outer membranes → simply “nuclei” floating in cytoplasm
    • As the cell membranes rupture, hydrolytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes are released, allowing the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week to “eat its way” into the uterine wall.
  • A layer of endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development (decidua functionalis) covers the invading blastocyst Blastocyst A post-morula preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Fertilization and First Week = implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week

Gastrulation

Overview of gastrulation

Gastrulation is the process by which the bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development develops into the trilaminar disc.

Note: This animation does not have sound.
  • Establishes all 3 primary germ layers:
    • Ectoderm (dorsal)
    • Mesoderm (middle)
    • Endoderm (ventral)
  • Occurs during the 3rd week ( memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment trick: 3rd week = 3 layers)
  • Process begins with formation of the primitive streak on the surface of the epiblast Epiblast Embryoblast and Trophoblast Development.
Process of gastrulation

Process of gastrulation:
Cells from the epiblast Epiblast Embryoblast and Trophoblast Development migrate down through the primitive streak and displace most of the hypoblast Hypoblast Embryoblast and Trophoblast Development cells, becoming the endoderm. Cells that remain in the middle become the mesoderm. Cells that remain in the epiblast Epiblast Embryoblast and Trophoblast Development layer become the ectoderm.

Image: “Germ Layers” by Phil Schatz. License: CC BY 4.0

Primitive streak and the primitive groove

  • Primitive streak: an area in the midline of the epiblast Epiblast Embryoblast and Trophoblast Development layer begins to thicken: 
    • Forms around day 16 of development 
    • Starts at the caudal end → extends < halfway down the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week toward the cranial end
    • Establishes the main body axis:
      • Cranial and caudal ends
      • Left and right
    • Primitive node: more prominent area at cranial end of primitive streak
  • Primitive groove: appears as small depression in primitive streak
  • Primitive pit: depression within primitive node that will develop into notochord
  • Fibroblast growth factor Fibroblast growth factor A family of small polypeptide growth factors that share several common features including a strong affinity for heparin, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. X-linked Hypophosphatemic Rickets 8 (FGF8):
    • Secreted by cells in the primitive streak/groove
    • Inhibits the production of adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies molecules holding the epiblast Epiblast Embryoblast and Trophoblast Development cells together
    • Without adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis epiblast Epiblast Embryoblast and Trophoblast Development cells can migrate
  • Prechordal plate: a compact area at the cranial end of the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week
Beginning of gastrulation

Beginning of gastrulation:
The primitive streak and primitive groove form in the bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development.

Image by Lecturio.

Epiblast Epiblast Embryoblast and Trophoblast Development migration

Migration of epiblast cells

Migration of epiblast Epiblast Embryoblast and Trophoblast Development cells through the primitive groove:
These epiblast Epiblast Embryoblast and Trophoblast Development cells displace the hypoblast Hypoblast Embryoblast and Trophoblast Development to become the endoderm and create a middle layer known as mesoderm. Epiblast Epiblast Embryoblast and Trophoblast Development cells that remain on the dorsal surface differentiate into ectoderm.

Image by Lecturio.

The trilaminar disc

  • Ectoderm: cells remaining in the epiblast Epiblast Embryoblast and Trophoblast Development layer (continuous with the amnion Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the amniotic fluid. Amnion cells are secretory epithelial cells and contribute to the amniotic fluid. Placenta, Umbilical Cord, and Amniotic Cavity)
  • Mesoderm: cells that invaginated beneath epiblast Epiblast Embryoblast and Trophoblast Development (middle layer)
  • Endoderm: cells that invaginated beneath the epiblast Epiblast Embryoblast and Trophoblast Development and replaced the hypoblast Hypoblast Embryoblast and Trophoblast Development
    • Embryonic endoderm (usually just called endoderm) → becomes primitive gut tube
    • Extraembryonic endoderm → lines secondary yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development
  • Secondary yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development: cavity between embryonic and extraembryonic endoderm
Layers of the trilaminar disc

Layers of the trilaminar disc

Image by Lecturio.

Formation of the chorionic cavity

Chorionic cavity

Formation of the chorionic cavity

Image by Lecturio.

Formation of the notochord

  • Notochord: chord-like structure that runs along the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week
  • Appears in 3rd week of development during gastrulation
  • Process of notochord formation:
    • Ectodermal cells invaginate in primitive pit → mesodermal cells
    • Mesodermal cells move cranially in midline until they reach the prechordal plate
    • Mesodermal cells create a tube-like structure
  • Function: induces overlying ectoderm to differentiate into the neural plate (start of neurulation)
  • Persists postnatally as the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles pulposus (soft gelatinous central portion of the intervertebral disk)
Formation of the notochord during gastrulation

Formation of the notochord during gastrulation.

Image by Lecturio.

Neurulation

Neurulation is the process by which ectoderm in the trilaminar embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week develops into the neural tube.

Note: This animation does not have sound.

Beginning in the 3rd week, a group of ectodermal cells progresses through the following structures:

  • Notochord: induces differentiation of ectodermal cells above it to form neural plate
  • Neural plate: thickening of ectoderm along the midline
  • Neural groove: a depression forms in the center of neural plate
  • Neural folds: 
    • Consists of cells forming lateral walls around neural groove, which elevate slightly above the rest of the ectoderm
    • The “uppermost” cells on the neural folds differentiate into neural crest Neural crest The two longitudinal ridges along the primitive streak appearing near the end of gastrulation during development of nervous system (neurulation). The ridges are formed by folding of neural plate. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the neural tube. Hirschsprung Disease cells, which form a number of different peripheral nervous structures.
  • Neural tube: 
    • The neural folds circle upward and meet in the midline, forming a tube
    • This tube is pulled below the outer layer of ectoderm → now known as the neural tube
    • Neural crest Neural crest The two longitudinal ridges along the primitive streak appearing near the end of gastrulation during development of nervous system (neurulation). The ridges are formed by folding of neural plate. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the neural tube. Hirschsprung Disease cells separate and are located between the neural tube and the ectoderm.
    • Cranial portion of neural tube: enlarges to become the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Caudal portion of neural tube: remains tubular, becomes the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy

Development requires folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12; folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 deficiency → neural tube defects Neural tube defects Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed NTD) to very severe malformations of the spine or brain (open NTD). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects

The process of neurulation

The process of neurulation:
Neural crest Neural crest The two longitudinal ridges along the primitive streak appearing near the end of gastrulation during development of nervous system (neurulation). The ridges are formed by folding of neural plate. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the neural tube. Hirschsprung Disease cells (green) are derived from the neural plate (gray), which folds upwards and inwards towards the midline to create the neural tube.

Image by Lecturio.

Derivatives of the Trilaminar Embryo

Ectoderm derivatives

  • Surface ectoderm (outer layer of ectoderm remaining after neurulation):
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, hair, and nails
    • Adenohypophysis Adenohypophysis The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the adenohypophyseal hormones that regulate vital functions such as growth; metabolism; and reproduction. Pituitary Gland: Anatomy (anterior pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types)
    • Lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy of the eye
    • Epithelial linings in the:
    • Glands:
      • Salivary 
      • Sweat
      • Mammary
  • Neural tube (CNS):
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy
    • Retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • Neural crest Neural crest The two longitudinal ridges along the primitive streak appearing near the end of gastrulation during development of nervous system (neurulation). The ridges are formed by folding of neural plate. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the neural tube. Hirschsprung Disease cells (PNS):
    • Autonomic nervous system Autonomic nervous system The ANS is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ANS consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System: Anatomy
    • Enteric nervous system Enteric nervous system Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. Autonomic Nervous System: Anatomy (in the GI tract)
    • Cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions
    • Schwann cells
    • Adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy
    • Melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions
    • Aorticopulmonary septum Aorticopulmonary septum Development of the Heart

Mesoderm derivatives

  • Muscle (all 3 types):
    • All skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology
    • Cardiac: heart
    • All smooth muscle (e.g., in bowel wall, bronchial walls, uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy, vessel walls)
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types, cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology, and connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • Blood and lymphatic vessels Lymphatic Vessels Tubular vessels that are involved in the transport of lymph and lymphocytes. Lymphatic Drainage System: Anatomy
  • Blood
  • Peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy, mesenteries, and ligaments in the abdominal cavity
  • Organs:
    • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy and ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy
    • Adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy
    • Spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy
    • Gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types ( testes Testes Gonadal Hormones and ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy)
    • Upper vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy

Endoderm derivatives

  • Endothelial lining of the respiratory tree
  • Endothelial lining and mucosal glands of the entire GI tract down to the pectinate line Pectinate line Rectum and Anal Canal: Anatomy in the anal canal ( memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment trick: endoderm is the enteral layer)
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy and biliary tree Biliary tree The bile ducts and the gallbladder. Gallbladder and Biliary Tract: Anatomy
  • Pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
  • Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy
  • Lower vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy
  • Thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy

Clinical Relevance

Abnormal gastrulation

Spontaneous abortion Spontaneous abortion Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks’ gestation. However, the layperson use of the term “abortion” is often intended to refer to induced termination of a pregnancy, whereas “miscarriage” is preferred for spontaneous loss. Spontaneous Abortion ( miscarriage Miscarriage Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks’ gestation. However, the layperson use of the term “abortion” is often intended to refer to induced termination of a pregnancy, whereas “miscarriage” is preferred for spontaneous loss. Spontaneous Abortion): abnormalities of gastrulation typically result in multiple congenital Congenital Chorioretinitis anomalies. These embryos are typically incompatible with life, and the result is a spontaneous loss of the pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, usually in the 1st trimester. 

Neural tube defects Neural tube defects Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed NTD) to very severe malformations of the spine or brain (open NTD). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects

Neural tube defects Neural tube defects Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed NTD) to very severe malformations of the spine or brain (open NTD). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects ( NTDs NTDs Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed ntd) to very severe malformations of the spine or brain (open ntd). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects): caused by the failure of the neural tube to close properly during embryologic development, potentially resulting in protrusion of neural tissue. Neural tube defects Neural tube defects Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed NTD) to very severe malformations of the spine or brain (open NTD). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects may involve the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy and/or cranium Cranium The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy and may be open (involving the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy and/or neural tissue) or closed (involving the bony vertebral column Vertebral column The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy). Prenatal diagnosis by ultrasonography and maternal α-fetoprotein level is common. Management of open NTDs NTDs Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed ntd) to very severe malformations of the spine or brain (open ntd). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects is mainly surgical. 

  • Open NTDs NTDs Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed ntd) to very severe malformations of the spine or brain (open ntd). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy:
    • Meningocele Meningocele A congenital or acquired protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. Neural Tube Defects: only meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy protrudes
    • Meningomyelocele Meningomyelocele Congenital, or rarely acquired, herniation of meningeal and spinal cord tissue through a bony defect in the vertebral column. The majority of these defects occur in the lumbosacral region. Clinical features include paraplegia, loss of sensation in the lower body, and incontinence. This condition may be associated with the arnold-chiari malformation and hydrocephalus. Neural Tube Defects: both meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy protrude (most common NTD)
  • Open NTDs NTDs Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed ntd) to very severe malformations of the spine or brain (open ntd). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects of the cranium Cranium The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy:
    • Cranial meningocele Meningocele A congenital or acquired protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. Neural Tube Defects: only meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy protrude
    • Cranial encephalocele Encephalocele Brain tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. Neural Tube Defects: both meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy and brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem/ cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy/ cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: Anatomy protrude 
    • Anencephaly Anencephaly A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. Neural Tube Defects: complete failure of cephalic neural tube to close, resulting in fully exposed fetal brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification (not compatible with life)
  • Closed NTDs NTDs Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed ntd) to very severe malformations of the spine or brain (open ntd). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects: midline defect of vertebral bodies without protrusion of meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy or neural tissue:
    • Spina bifida occulta Spina bifida occulta A common congenital midline defect of fusion of the vertebral arch without protrusion of the spinal cord or meninges. The lesion is also covered by skin. L5 and s1 are the most common vertebrae involved. The condition may be associated with an overlying area of hyperpigmented skin, a dermal sinus, or an abnormal patch of hair. The majority of individuals with this malformation are asymptomatic although there is an increased incidence of tethered cord syndrome and lumbar spondylosis. Neural Tube Defects: without a subcutaneous mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Lipomeningocele Lipomeningocele Neural Tube Defects or lipomyelomeningocele Lipomyelomeningocele Neural Tube Defects: with a subcutaneous mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast

References

  1. Carlson, B.M. (Ed.). (2018). Human Embryology and Developmental Biology, 6th ed. Elsevier.
  2. Sadler, T. W. (2018). Langman’s Medical Embryology, 14th ed. Lippincott Williams & Wilkins.
  3. Muhr, J. (2021). Embryology, gastrulation. StatPearls. Retrieved October 29, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/22120/ 
  4. OpenStax College. (n.d.). Anatomy and physiology. OpenStax CNX. Retrieved October 29, 2021, from https://philschatz.com/anatomy-book/contents/m46319.html 

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