Question

Limb development involves several feedback loops which are coordinated and work to sustain each other.

A. WHAT are those feedback loops?

B. HOW do they interact/HOW and WHAT are they coordinating?

C. If these loops positively regulate each other then how does embryonic limb bud formation end?

Answer 1

Answer- Feedback loop system is a controlling system in our body in which function of one part depends upon output of another part. And both of these parts are controlling each other.

A. Answer-

The feedback loop system of vertebrate limb development is controlled by two key signalling centres drive vertebrate limb development: the apical ectodermal ridge (AER) and the zone of polarising activity (ZPA).

B Answer-

Embryological manipulations of the chick limb bud defined the AER as essential for the proximal-to-distal (shoulder-to-digits) outgrowth of the limb and the ZPA as the source of a morphogen that patterns anterior-to-posterior (thumb-to-pinky) axis of the limb. It may seem intuitive that the development of these two axes should be linked, as this would allow for the production of reproducible pattern: a perfect limb every time.

The ZPA is operationally defined as a region of posterior mesoderm that, when transplanted into the anterior mesoderm of another limb, can induce mirror-image duplications of the AP axis of the limb. However, it is clear from these experiments that the resulting limb duplications are also appropriately patterned along the PD axis, indicating that the grafted tissue can direct patterning along both axes. In addition, it is known that ZPA grafts can only induce limb duplication when grafted close to the AER and that the polarising activity found in this mesoderm diminishes a few hours after and AER is extirpated. This evidence points to an important role for the ridge in promoting polarising activity, and we discuss here how FGF signalling that is central to this function.

Sonic hedgehog (Shh) is expressed in the ZPA and, like the ZPA, Shh can induce mirror-image AP axis duplication when supplied to the anterior mesoderm of another limb bud. It has been shown that Shh induces the expression of FGF4 in the anterior AER; normally, FGF4 expression is restricted to the posterior ridge. In the mesoderm, Shh activates the expression of BMP2 and HoxD11. However, when Shh is presented to mesoderm cells that are some distance from the AER, it fails to induce the expression of these targets, pointing to a requirement for the gene products (such as FGF4) that are induced by Shh and are present in the AER. It is thought that AER-derived FGF signalling acts on the mesoderm and renders it competent to respond to Shh signalling.

C. Answer-

If these loops coordinately and positively interact each other than developing limb bud occurs as mesenchymal cells from the lateral plate mesoderm. The mesoderm cells in the limb bud will eventually differentiate into the developing limb’s connective tissues, such as cartilage, bone, and tendon.