Control of cranial neural crest fate decision by Hox genes

HOX基因控制着发育中胚胎前后轴的形态发生。编码的蛋白质作为转录因子发挥作用，但它们的目标基因在脊椎动物中大多未知。这一建议的目的是鉴定Hoxa2直接调控的基因，以控制脊椎动物胚胎的瞬时细胞群--颅神经脊的分化。这些胚胎细胞可以产生许多衍生物，但它们形成骨骼组织的能力受到Hox基因的抑制，特别是Hoxa2基因。Hoxa2基因在脑神经脊区诱导表达的突变小鼠的产生和分析是鉴定Hoxa2基因在脑神经脊区分化中调控基因的关键。这个模型系统的设计是为了最终确定Hoxa2下游的即时事件的特征。所获得的结果将有助于深入了解HOX基因如何调控脊椎动物胚胎的形态发生，并有助于理解支配面部骨骼形成的机制。这项工作将在曼彻斯特大学进行。

Hox genes control morphogenesis along the antero-posterior axis of the developing embryo. The encoded proteins act as transcription factors, but their target genes are mostly unknown in vertebrates. This proposal is aimed at the identification of the genes directly regulated by Hoxa2 in the control of the differentiation of the cranial neural crest, a transient cell population of the vertebrate embryo. These embryonic cells can give rise to many derivatives, but their capacity to form skeletal tissues is inhibited by Hox genes and in particular by Hoxa2. The key to the identification of the genes controlled by Hoxa2 in the differentiation of the cranial neural crest will be the generation and the analysis of mutant mice with inducible expression of Hoxa2 in the cranial neural crest. This model system is designed to conclusively characterize the immediate events downstream of Hoxa2. The results obtained will give insights into how Hox genes regulate morphogenesis in the vertebrate embryo and help to understand the mechanisms that govern the formation of the facial skeleton. The work will be carried at the University of Manchester.