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Practice question

Question

What happens when Islet1 is knocked out in the lateral plate mesoderm?

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Explanation

Hindlimb field specification requires LIM-homeodomain transcription factor Islet1 in posterior lateral plate mesoderm. Islet1 promotes nuclear accumulation of beta-catenin activating beta-catenin pathway and directly drives Fgf10 expression initiating hindlimb bud. Early inactivation of Islet1 via conditional deletion in lateral plate leads to failure of Fgf10-Fgf8 feedback establishment selectively in hindlimb, resulting in complete hindlimb agenesis while forelimbs remain intact. It also regulates Hand2-Shh pathway posteriorly. Therefore Islet1 acts as hindlimb-specific initiator upstream of beta-catenin and represents missing regulatory link distinguishing hindlimb from forelimb.

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