Role of Pitx1 Upstream of Tbx4 in SpeciÞcation of Hindlimb Identity

In spite of recent breakthroughs in understanding limb patterning, the genetic factors determining the differences between the forelimb and the hindlimb have not been understood. The genes Pitx1 and Tbx4 encode transcription factors that are expressed throughout the developing hindlimb but not forelimb buds. Misexpression of Pitx1 in the chick wing bud induced distal expression of Tbx4, as well as HoxC10 and HoxC11, which are normally restricted to hindlimb expression domains. Wing buds in which Pitx1 was misexpressed developed into limbs with some morphological characteristics of hindlimbs: the ßexure was altered to that normally observed in legs, the digits were more toe-like in their relative size and shape, and the muscle pattern was transformed to that of a leg. In most respects the genetic systems controlling limb development act equivalently in the chick forelimb (wing) and hindlimb (leg) buds. How-ever, as is true for the human arm and leg, the chick wing and leg have very different mor