Practice question

Hindlimb bud initiation integrates multiple transcription factors forming coherent feed-forward network upstream of outgrowth. Islet1, a LIM-homeodomain protein expressed early in posterior lateral plate, maintains Pitx1 and Tbx4 expression, Pitx1 directly drives Tbx4 and hindlimb enhancer of FGF10, Tbx4 directly activates FGF10. Knockouts of any single factor reduce hindlimb formation substantially, combined loss abolishes budding and produces amelia with absent hindlimbs. Islet1 also maintains FGF10 independently via Ldb1 cofactor recruitment. Thus early hindlimb initiation relies cooperatively on Islet1, Pitx1 and TBX4, making all factors essential participants upstream of loop.