Finger or toe: the molecular basis of limb identity

Abstract

Despite their obvious similarities, the forelimbs and hindlimbs of tetrapod vertebrates have evolved distinct structural elements to carry out their discrete functions. Many genes required for limb initiation and patterning are involved in regulatory networks common to both limb-types. Other genes are differentially expressed between forelimb and hindlimb, and have been implicated in the initiation of limb bud outgrowth and the specification of limb-type identity. In this review, I will discuss the current understanding of how genes that control limb identity interact with regulatory networks common to both appendages to produce the fingers of the hand and toes of the foot.

MDGA1, an IgSF molecule containing a MAM domain, heterophilically associates with axon- and muscle-associated binding partners through distinct structural domains

“…MDGA1 does not appear to be generally involved in this process, because some of the lumbar LMCm neurons apparently do not express MDGA1. However, it is still possible that MDGA1 might be required for the proper segregation of these motor neurons at the base of the forelimbs and at a specific choice point in the hindlimbs, since these limbs are differentially specified (Logan, 2003), and each plexus might face somewhat different circumstances.…”

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

“…Tbx4 and Tbx5 play a cardinal role in initiating limb outgrowth. Furthermore, Tbx5 is specifically expressed in the forelimb field and Tbx4 in the hindlimb, and the genes have been proposed to specify fore-vs. hindlimb identity (reviewed in Logan, 2003). This finding, however, is not supported by an elegant experiment leading to expression swapping between Tbx5 and Tbx4 in the forelimb (Minguillon et al, 2005).…”

Microarray analysis of Tbx5‐induced genes expressed in the developing heart

“…Mutations in TBX5 are associated with Holt-Oram syndrome (HOS), a congenital disorder characterized by limb malformations, cardiac septal defects, and conduction system anomalies (Basson et al, 1997;Li et al, 1997). Consequently, the function of Tbx5 in the formation of the heart and limbs has been the subject of several investigations (Logan, 2003;Plageman and Yutzey, 2005). During development, tbx5 is expressed in the embryonic heart and forelimbs, suggesting that altered Tbx5 function at these locations underlies abnormal development (Chapman et al, 1996).…”