Control of cranial neural crest fate decision by Hox genes

Hox基因沿发育中的胚胎的前后轴控制形态发生。编码的蛋白质作为转录因子，但它们的靶基因在脊椎动物中大多是未知的。本研究旨在鉴定Hoxa2直接调控的调控颅神经嵴分化的基因，颅神经嵴是脊椎动物胚胎中一种瞬时细胞群。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，特别是Hoxa2的抑制。鉴定Hoxa2在颅神经嵴分化中所控制的基因的关键将是在颅神经嵴诱导表达Hoxa2的突变小鼠的产生和分析。该模型系统旨在最终表征Hoxa2下游的直接事件。获得的结果将深入了解Hox基因如何调节脊椎动物胚胎的形态发生，并有助于理解控制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.