Twist functions in mouse development.

The remarkable similarity in the profile of genetic activity and the frequent association of developmental defects of limb and craniofacial structures in mouse mutant and hereditary disorders point to the possibility that the development of the head and limb involves common morphogenetic mechanisms. Our recent studies on the impact of the loss of Twist function has highlighted the essential role of the basic helix-loop-helix transcription factor encoded by this gene on the development of both body parts. We have summarized in this review our findings on the molecular pathways that are disrupted in Twist mutant mouse embryos. Our results revealed an evolutionarily conserved function for Twist in mesodermal differentiation, and previously unrecognised effects of the loss-of-function mutation of this gene in the outgrowth and patterning of the limb and branchial arches,and neural crest cell migration. An important outcome of our study is the demonstration of a differential requirement for Twist in forelimb versus hindlimb development, and its functional interaction with Gli3 in specifying anterior digit formation. Further evidence of the conservation of the function of Twist in different species is highlighted by similarity in the spectrum of potential downstream targets and interacting genes of Twist that have been identified by genetic, functional and microarray analysis.