Understanding limb patterning: the last two decades

Abstract

A fundamental question in biology is how an organ or tissue is built, how a cluster of progenitor cells ends up producing a perfect and fully functional limb. While the fundamental question remains unchanged, the way to tackle it has moved in the past few decades from the traditional embryonic experimental manipulation to more molecular and genetic approaches and lately to functional genomics. The limb begins its development when the limb progenitors detach from the epithelial somatopleure and accumulate under the surface ectoderm where they induce the apical ectodermal ridge (AER), a crucial signaling center for limb outgrowth. Two aspects of limb development will be predominantly discussed: the induction of the AER and the mechanisms by which the limb progenitors acquire progressively more distal fates. The former involves the function of Sp6 and Sp8, two members of the Sp family of transcription factors expressed in the limb ectoderm, and that are at the crossroad between proximo-distal and dorso-ventral patterning. The later involves the analysis of the temporal transcriptome of the distal limb progenitors, to identify the gene expression sets characteristic of their distinct proximo-distal specification states, and of the AER, to get information on the genetic control of its development, maturation and regression. The goal is to increase our understanding of the mechanisms regulating the orderly and progressive differentiation of the limb.