alx1 homeobox gene and craniofacial development

脊椎动物面部的发育是一个非常动态和复杂的过程，需要严格调控脑神经脊细胞的生长、迁移、融合和图案化。因此，面部畸形是最常见的畸形之一，占人类先天性缺陷的三分之一。这些缺陷中的一类是额鼻发育不良(FND)，表现出从轻微的眼睛过度调节到严重的面裂等广泛的临床症状。虽然大多数FND病例被认为是散发性的，但ALX-FND是少数有明确遗传原因的FND之一，由Alx同源框基因(ALX1、ALX3或ALX4)突变引起。然而，Alx基因并不只涉及人类FND。最近的研究表明，缅甸猫头的形态变化也是由Alx基因突变引起的。此外，ALX1基因已被证明与达尔文雀喙的进化多样性有关。这些结果表明，Alx同源框基因在脊椎动物头面部的发育和进化中起着重要作用，但关于Alx基因如何参与脊椎动物头面部发育的详细分子机制还知之甚少。在这方面，我们在最近的一篇论文中报道了斑马鱼ALX1基因的一个新功能，它调节脑神经脊细胞(CNCS)的迁移，从而参与颅面发育。基于这些结果，本项目旨在了解Alx同源框基因调控的细胞和分子机制，包括CNCs迁移的分子机制及其对头部形态的影响，为脊椎动物头部区域的发育和进化提供重要的见解。因此，这项研究符合BBSRC的职权范围。

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.