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Question

Which gene is critical for forelimb specification in limb development?

Options

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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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