Development of the Vertebrae

00:01 Hello. Welcome to development of the vertebrae.

00:03 This is the first talk.

00:04 We´re gonna start with trilaminar embryo and actually follow the development of a set of structures pretty much from start to its almost mature structural appearance at the time of birth.

00:16 So the back and limbs are very complicated structures.

00:19 They support the body´s weight and protect the spinal cord but also have to allow movement to occur and if that weren´t challenging enough, these structures have to change during development to allow growth.

00:30 So in the process, we´re gonna see how the vertebrae form but take on different confirmations as they get larger and larger but still protect the spinal cord and the limbs that grow off the body will be discussed after we discuss the back and will follow not only the bony formation but also, the muscles that are going to allow coordinated movement to occur.

00:51 And once they´ve formed, we´ve also got to allow them to grow and develop as we do.

00:57 Now, recall that the sclerotome has migrated around the neural tube and created a loose model of the vertebrae and outside of the sclerotome, we have the myotome to form muscle and the dermatome to form the dermis of the skin and we need to get nerves to and from the dermatome and myotome but for that to happen, nerves have to pierce the sclerotome and the sclerotome´s pretty tough.

01:21 So nerves reach it in a relatively unique way.

01:24 Each sclerotome develops little fissures inside of it called von Ebner´s fissures and these fissures fully separate each sclerotome and actually allow it to migrate.

01:37 So portions of one sclerotome will fuse to a portion from its neighbor and that´s gonna create a channel that allows the nerve to exit the spinal cord and reach the myotome and then, the dermatome.

01:49 And once those neighboring portions of sclerotome have met, they are then going to fuse and form the actual mature vertebrae.

01:59 So that´s what allows nerves to get to and from the dermatome and the myotome and allows the sclerotome to take up its normal appearance of a vertebra.

02:10 So as that happens, the portion that remains in between adjacent the vertebra is going to develop into the intervertebral discs.

02:18 Now at the core of each intervertebral disc is a region called the nucleus pulposus.

02:25 Now, the nucleus pulposus is a shock absorber for our body and allows our vertebra to compress and relax without too much trauma but it´s the only remnant we have of the notochord.

02:38 So even though the notochord was ridiculously important during development, in the adult, the only remnant of it is the nucleus pulposus at the core of the intervertebral disc.

02:47 The outer most layer of the intervertebral disc is called the annulus fibrosus and it also comes from the schlerotome.

02:54 So now, we have a lose model made of mesenchyme.

03:00 Undifferentiated cells out of each vertebra surrounding the spinal cord with the notochord at its center.

03:07 Now, this grouping of cells is a little tough but it needs to be tougher for the body to have support as it develops.

03:14 And for that region, we get chondrification centers forming inside this model.

03:20 These chondrification centers will create cartilage which is a bit more substantial than the mesenchyme, not quite as strong as bone, and certain animals like fish will often retain cartilage only vertebra.

03:34 So we start with mesenchyme, we move to chondrification to create a cartilage and then, once the cartilage is in place, we will have ossification centers form that will convert the cartilage into bone.

03:48 So primary ossification centers in the vertebra are going to form in the vertebral body and then, the pedicels, and that ossification will then, spread outward replacing cartilage with bone.

04:00 The last portion of each vertebra to be ossified is gonna be the spinous process.

04:06 So as it´s forming, other secondary centers of ossification are going to be present and they´re going to join with the primary centers.

04:16 These secondary centers are located on either side of the vertebral body called the anular epiphysis in the transverse processes and the spinous process and just recall that because the spinous process is the last portion to ossify, it can be affected by spina bifida.

04:33 Now, one thing I want you to note is this process that formed the vertebra is called endochondral ossification and we´re gonna see it in detail in the limbs but the short story for now is that it´s the process by which mesenchyme becomes cartilage, becomes bone.

04:50 So it´s a three step process to the creation of bone.

04:52 The ribs are also gonna develop off of the sclerotome and as the somatopleure wraps around the body and forms an anterior body wall, it´s going to pull the portion of the sclerotome with it that´s gonna form the ribs.

05:07 It´s gonna extend further and further anteriorly along with that portion of the somatopleure and when it meets on the anterior body wall, the leading edge contains at its core, some condensations that are gonna become the sternum.

05:22 So these sternal bars, we´ve got one on the left and one on the right, are going to fuse as the somatopleure fuses and no big surprise, it´s going to form the sternum, its upper portion, the manubrium, and its slower portion, the xiphoid process.

05:39 The sternal bars fuse form superior to inferior and pull the ribs forward so that we wind up with a completely enclosed thorax.

05:49 Once that´s happened, we will get ossification centers within the sternal bars that convert it to bone and there are multiple ossification center that form and allow that to occur and when we´re done, we have the manubrium sternum and xiphoid process anchoring the ribs at the anterior most portion of our body wall.

06:11 Now, the process of endochondral ossification creates these vertebra but you´ll notice if you know your anatomy that the cervical vertebrae look different from the thoracic vertebra and they look very different from the lumbar, sacral, and coccygeal vertebra.

06:29 The reason these vertebra look different even though the same processes create them is because of the expression of Hox genes or Homeobox genes.

06:38 You see these genes come into play when you have variation in a structure.

06:42 When you have the formation of the upper and lower limbs, these are the genes that allow your fingers to be different from your humerus.

06:50 And in the back, they create the difference between the cervical, thoracic, lumbar, and sacral vertebra.

06:57 So the further inferiorly we go, the more members of the Hox gene family are expressed and this is what drives the differences in appearance between each region.

07:07 So the spectrum of Hox genes is actually gonna be what makes each region distinctive and slight variations in this process can create some slight abnormalities in the vertebra.

07:20 The dynamic process of forming the vertebra and ribs is very tightly regulated by the Hox gene family and because there are so many things going on in this process, there are many things that can go wrong.

07:32 Amongst those would be the formation of a hemivertebra where sclerotome doesn´t just form a single vertebral body but has more than one vertebral body that´s shown in the illustration here.

07:44 We can also have what´s called a butterfly vertebra where it´s been compressed and on the opposite extreme, we have a fusion of the vertebra created from more than one sclerotome fusing and instead of two separate vertebra, we´ve got one.

07:58 Now, as we have explained, Hox genes expression is responsible for the differentiation of the different vertebra depending on the level of the vertebra.

08:08 There are currently more than 30 Hox genes that are related to this.

08:13 However, mutations only in 10 Hox genes in humans had been associated with vertebral body malformations, for example, a mutation in Hox C4 will result in T2 to T11 vertebral malformations.

08:30 Mutations in Hox A5 are associated with the development of a C7 cervical rib.

08:37 So instead of ribs starting at T1, you may have a rib or portion of a rib developing off the 7th cervical vertebra.

08:47 And if the ossification process is disrupted because the caudal neuropore hasn´t closed, the spinous processes are unable to meet on the midline and you wind up with the various types of spina bifida that were demonstrated when we discussed neurulation.

09:04 Another problem that can occur is if the sternal bars incompletely fuse or the ossification centers inside the sternal bars don´t do their work the way we´d expect, there can be small sternal defects.

09:17 Now, on the small side, you have sternal foramina and on the large side, you can have large sternal clefts.

09:24 And these may be problematic if they´re especially enlarged but small sternal foramina may be completely clinically invisible and not cause problems only be noted on x-ray.

09:35 Because the sternum zips closed from a superior to inferior direction, it´s not uncommon for the inferior most portion of it to remain separate and give what´s called a bifid or split xiphoid process.

09:49 These again are not clinically important but may be noted on x-ray.

09:54 But just remember, a split xiphoid process is not indicative of a fracture, it´s just a remnant of development.

10:01 Alright, thank you very much and we´ll follow by going into the development of the limbs.