Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity

In spite of recent breakthroughs in understanding Limb patterning, the gene tic factors determining the differences between the forelimb and the hindli mb have not been understood. The genes Pitx1 and Tbx4 encode transcription factors that are expressed throughout the developing hindlimb but not forel imb buds. Misexpression of Pitx1 in the chick wing bud induced distal expre ssion of Tbx4, as well as HoxC10 and HoxC11, which are normally restricted to hindlimb expression domains. Wing buds in which Pitx1 was misexpressed d eveloped into Limbs with some morphological characteristics of hindlimbs: t he flexure was altered to that normally observed in legs, the digits were m ore toe-like in their relative size and shape, and the muscle pattern was t ransformed to that of a Leg.