Limb Forming – Musculoskeletal System Development

by John McLachlan, PhD

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    00:01 to be. So, how can we explore how these elements are formed ? A very successful experimental model has been the developing limb for a variety of reasons. One is that the limb is not essential to life. So, experimental manipulations could be done on the limb during the course of development without killing the embryo itself. A useful developmental model has been the developing chick of the domestic hen. So many studies had been carried out on this, although, as I say, we know that the mechanisms and signals are universal, so, what we learned from this applies just as well to humans. But in addition, limb development is significant in its own right, because it’s one of the most common kinds of developmental abnormality found in humans. The limb buds actually first appear as bulges in the flank of the embryo and they grow as bulges, which are composed of mesoderm covered over by a layer of ectoderm.

    00:56 Into these developing bulges will grow nerve cells from the neural tube, neural crest cells which will give rise to a variety of tissues including pigment cells, muscle cells from the somite, and blood vessel cells from the blood vessels. So eventually, they will all migrate into the growing limb bud as it develops, as it grows out from the flank. Let’s look at the flank of an early embryo in a scanning electron micrograph view and you can see the limb buds are forming here. Particularly obvious is the fore limb bud, the arm bud, and covered in ectoderm, as I say. But at the very tip of the limb, the ectoderm is raised into a ridge. This is known as the apical ectodermal ridge or AER. It turns out that this ridge of ectoderm is actually highly significant in inducing the outgrowth of the limb itself.

    01:51 If we look at it in close up, you can see the ridge of ectoderm at the tip of the limb bud.

    01:58 Now, why does it form in this particular position? Well, the back part of the embryo is expressing genes for dorsal areas, and the lower part is expressing genes for ventral areas. So dorsal and ventral genes, and where they meet, that’s where the apical ectodermal ridge forms. So plainly, these gene interactions are inducing the ectoderm to form this ridge-like structure in this particular place. One of the most relevant genes involved here is called radical fringe. Once the apical ectodermal ridge is formed, it then produces other developmental signals, such as fibroblast growth factors, and this help the limb to begin the process of growing out. If we were to remove the apical ectodermal ridge experimentally, it will lead to a loss of outgrowth of the limb, but in particular ways. So when the apical ectodermal

    About the Lecture

    The lecture Limb Forming – Musculoskeletal System Development by John McLachlan, PhD is from the course System-Specific Embryology with John McLachlan.

    Author of lecture Limb Forming – Musculoskeletal System Development

     John McLachlan, PhD

    John McLachlan, PhD

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