Embryonic Limb Development and Underlying Mechanisms

Subject: Sciences
Pages: 1
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The three axes of limb development are proximodistal, dorsoventral and anteroposterior. The proximodistal axis phase refers to the development of the limb from its tip to where it connects to the body. The apical ectodermal ridge (AER) is first formed at the region where FGF10 (fibroblast growth factor 10), which is a signalling molecule, is induced. Thereafter, the AER produces two other signalling molecules FGF4 and FGF8. The function of the FGF is to trigger the proliferation and outward growth in the mesenchyme that lies beneath. The developing limb along this axis has three parts namely stylopod, zeugopod and autopod.

The dorsoventral axis refers to the back of the spinal column to the front of the belly. The patterning of muscles occurs at this stage to form the ventral muscles or flexors and dorsal muscles or extensors. The dorsal ectoderm holds the dorsoventral signalling centre. The key morphogen that is involved in this process is Wnt, which is produced by dorsal ectoderm cells. Wnt triggers the expression of Lmx1, a homeobox gene in the surrounding mesoderm next to the dorsal face. Conversely, En1, another homeobox gene is expressed in the ventral ectoderm.

The anteroposterior axis denotes limb development from the head region to the opposite side of the body. During this phase, the zone of polarizing activity (ZPA) produces a sonic hedgehog (SHH) and determines the anteroposterior axis of the limb bud. SHH is crucial to the activity of ZPA. The continuous production of SHH is sustained by FGF.