Which of the following describes the function of PITX1 in limb development?
PITX1 is a paired-type homeodomain transcription factor restricted to hindlimb mesenchyme, serving as master hindlimb identity regulator throughout development. It directly activates TBX4 expression and represses forelimb genes, controlling hindlimb-specific characteristics including elongated femur shape, patella formation, tendon pattern and Pitx1-dependent hindlimb muscle via Tbx4-FGF10 axis and Hox genes. Transgenic loss or Pitx1 mutant mice show partial forelimb-like transformation of hindlimbs, altered knee articulation and clubfoot phenotypes. It does not maintain FGF8 directly, inhibit forelimb growth globally, or block Wnt signaling. Its role is activating hindlimb-specific program.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: PITX1 activates hindlimb-specific gene program.