alx1 homeobox gene and craniofacial development

The development of the vertebrate face is a remarkably dynamic and intricate process, requiring the tightly regulated growth, migration, fusion and patterning of cranial neural crest cells (CNCs). For this reason, facial malformations are among the most common, accounting for one third of human congenital defects. One well-documented class of these defects is frontonasal dysplasia (FND) displaying a broad range of clinical symptoms from mild ocular hypertelorism to severe facial cleft. Although most FND cases are considered sporadic, ALX-FND is one of the few FNDs with an established genetic cause, and cause by the mutations within Alx homeobox genes (Alx1, Alx3 or Alx4). However, Alx genes are not only involved in human FNDs. Recent studies have shown that morphological changes in the head of Burmese cats are also caused by mutations in the Alx genes. Moreover, Alx1 gene has been shown to related to the evolutionary diversification of Darwin's finches beak. These results indicate that the Alx homeobox genes are a major player in the development and evolution of the craniofacial region of vertebrates.
However, little is known about the detailed molecular mechanism of how the Alx genes are involved in the development of the craniofacial region of vertebrates. In this regard, we reported in a recent paper a new function of the zebrafish alx1 gene that regulates the migration of cranial neural crest cells (CNCs) and, as a result, is involved in the craniofacial development. Based on these results, this project aims to understand the cellular and molecular mechanisms underlying CNC migration and craniofacial development regulated by the Alx homeobox gene.
The outcome of this study will provide significant insights into the development and evolution of the vertebrate head region, including the molecular mechanisms of CNCs migration, which are still largely unknown, and their effects on head morphology. As such, this study fits within the BBSRC's remit.