Practice question
Question
Which gene is critical for forelimb specification in limb development?
Explanation
Forelimb identity is encoded by TBX5 restricted to rostral lateral plate mesoderm downstream of Hoxb4 Hoxb5 and retinoic acid signaling. TBX5 activates a forelimb-specific enhancer of FGF10 and Wnt2b, triggering epithelial-mesenchymal signaling cascade leading to bud outgrowth and AER induction via Wnt3a. Loss of Tbx5 abolishes forelimb formation entirely, while ectopic Tbx5 expression in hindlimb field can induce forelimb-like features including wing-type morphology. TBX4 performs analogous hindlimb function, Pitx1 reinforces hindlimb character, Islet1 contributes early to both fields. Thus TBX5 is master forelimb specifier.
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