Reconstructing the history of human limb development: Lessons from birth defects

A major goal of biology has been to understand the developmental mechanisms behind evolutionary trends. This has led to a growing interest in studying the molecular basis of the evolution of developmental programs such as tho se mediating the diversification of tetrapod limbs. Over the last 10 y, it has become clear that the genes and general developmental programs used to build a limb are strongly conserved among widely disparate species. This fi nding suggests that altered regulation of the timing and locations of devel opmental events may be responsible for the morphologic variation observed a mong some species. However, genetic analyses of the regulatory regions of g enes controlling vertebrate developmental programs are very limited. Charac terization of the genetic basis of human birth defects of the limb provides an opportunity to dissect the developmental programs used to modify the ar chitecture of the hominoid limb. This may allow us to assess the relative c ontributions of altered gene regulation to morphologic variation among spec ies and reconstruct the evolutionary history of the hominid limb. Such insi ght is also important because morphologic differences in the hominid upper limb have been correlated with the use of tools, and tool making is often r egarded as the milestone that marked the emergence of the genus Homo.