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#limb initiation

2 public questions tagged with this topic.

Limb Development -l

Which experiment demonstrated that FGF10 is required for limb initiation?

Essential requirement for FGF10 in limb initiation was proven by generating FGF10-null mice which exhibit complete agenesis of forelimb and hindlimb buds, while flank lateral plate mesoderm remains present and expresses Tbx markers initially. Implantation of FGF10-soaked heparin beads into mutant flank rescues apical ridge induction evidenced by restored Wnt3a and FGF8 expression in overlying ectoderm and partial bud outgrowth. Overexpression of Wnt7a influences dorsoventral patterning, ridge removal tests maintenance, blocking RA synthesis expands fields, but only FGF10 ablation prevents initiation throughout development.

Ref: Nature Reviews Genetics: FGF10 knockout mice lacking limb buds and bead rescue experiments.

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Limb Development -ll

Which transcription factor is involved in early hindlimb bud initiation?

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.

Ref: Kawakami et al., PNAS 2011, Gilbert Chapter 20: Islet1-Pitx1-Tbx4 network in hindlimb.

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