Limb Outgrowth – Musculoskeletal System Development

by John McLachlan, PhD

Questions about the lecture
My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides 19 Musculoskeletal System Development McLachlan.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:00 to a loss of outgrowth of the limb, but in particular ways. So when the apical ectodermal ridge is removed, what happens is that limb is truncated at a certain level. So at early stages, you may end up with half a humerous. Later on, you may interrupt the development of the radius and ulna, then the wrist, and then finally, the fingers and the elements that are present will grow to normal size. It’s not that they are smaller as a consequence, it’s as if you’ve stopped the process of distalization of outgrowth. And you can reinforce this idea by taking the apical ectodermal ridge that you’ve removed, and grafting it somewhere else on the flank of the developing embryo. When one does that, what you’ll observe is that an extra limb grows out. So the apical ectodermal ridge can induce the outgrowth of a new limb in an ectopic position. So plainly, the apical ectodermal ridge is highly significant, and the tissue signals are a valuable clue as to what controls the course of morphogenesis of the skeleton and of the muscles. That accounts for the axis from proximal to distal, from the shoulder to the tips of the fingers but there’s also an axis from anterior to posterior, from the thumb to the little finger site.

    01:18 And we can ask what controls that particular axis. If we look at the posterior margin of the limb, the limb margin towards the tail, there’s a little group of cells there undistinguished by any visible features. They look like all the other cells, but they have a particular property, and that is that if you remove them and graft them to the anterior margin of another limb bud, then the limb that develops will be a mirror image reduplication. In the illustration shown, then you can see that there are a total of five fingers, and since this is a chick embryo, this is a mirror image reduplication of both the midpoint. The two bones that are present in the mid-arm are actually two copies of the ulna, not a radius and ulna, as you would normally find and therefore, this little zone of cells has somehow signaled to create this axis from anterior to posterior, and the grafts of the anterior region has brought about an extra limb, an image, a mirror image reduplication of the limb. Therefore, it must be significant for creating, controlling the development of this axis of the limb.

    02:30 We can also mimic this effect by grafting in a little bead soaked in retinoic acid, which is a vitamin A precursor, and is well known as a developmental signal. So we don’t even need the cells to bring about these mirror image reduplications. As we’ll see, this idea is significant later in human development also. So, what’s going on here? One thing that’s been proposed as an idea is that those cells, the zone of polarizing activity, the ZPA cells, are actually creating a gradient of something. In this sketch, I’ve outlined a limb bud, and a little dot stone in the posterior margin is where the ZPA probably is located. And I’ve also sketched in a potential gradient spreading across the limb as a result. On that gradient, there are thresholds, where the gradient substance whatever it is, is high, then one gets a digit four. When it is lower, then one gets a digit three. And the lowest level in a chick limb gives you a digit two. Grafting a ZPA to the other margin of the limb creates a U-shaped distribution of the gradient substance, and you can see that that would be interpreted as a 4,3,2-2,3,4 reduplication in the chick embryo. Therefore, this looks like a plausible kind of explanation for what’s going on, the nature of the tissue signaling that’s taking place from the ZPA. Indeed, now we’ve been able to identify the genes that are involved.

    About the Lecture

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

    Author of lecture Limb Outgrowth – Musculoskeletal System Development

     John McLachlan, PhD

    John McLachlan, PhD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star