alx1 homeobox gene and craniofacial development

alx1同源盒基因与颅面发育

• 批准号: 2441472
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2441472
• 关键词: alx1; homeobox; gene; 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.

脊椎动物面部的发育是一个非常动态和复杂的过程，需要颅神经嵴细胞（CNCs）的严格调控的生长，迁移，融合和图案化。因此，面部畸形是最常见的，占人类先天性缺陷的三分之一。这些缺陷的一个有据可查的类别是额鼻发育不良（FND），其显示从轻度眼距过宽到严重面裂的广泛临床症状。虽然大多数FND病例被认为是散发性的，但ALX-FND是少数几种具有既定遗传原因的FND之一，并且是由Alx同源盒基因（Alx 1，Alx 3或Alx 4）内的突变引起的。然而，Alx基因不仅参与人类FND。最近的研究表明，缅甸猫头部的形态变化也是由Alx基因突变引起的。Alx 1基因与达尔文雀喙的进化多样性有关。这些结果表明，Alx同源盒基因在脊椎动物颅面区的发育和进化中起着重要作用，但关于Alx基因参与脊椎动物颅面区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alx 1基因的一个新功能，该基因调节颅神经嵴细胞（CNCs）的迁移，因此参与颅面发育。基于以上研究结果，本项目旨在了解Alx同源盒基因调控CNC迁移和颅面发育的细胞和分子机制，为深入研究脊椎动物头部的发育和进化，包括CNC迁移的分子机制及其对头部形态的影响提供重要的理论依据。因此，这项研究符合BBSRC的职权范围。