RNA dynamics in the developing mouse face

颅面形态发生是一个复杂的过程，需要六个不同的面部突起协调增殖、运动和分化。这一过程的复杂性使其容易受到环境和遗传的干扰，因此颅面畸形是最常见的出生缺陷之一。面部突出由单层外胚层包裹着神经嵴和中胚层来源的间充质细胞组成。这一小群外胚层细胞发出的信号指导和协调底层间质的行为，从而促进面部形态的形成。改变这些信号过程和组织相互作用的操作对面部发育有严重后果，导致各种类型的医学上重要的畸形，包括口面部裂。因此，外胚层基因动力学的详细知识是面部发育总体描述的重要组成部分。在这项提议中，一个多学科的团队聚集了颅面生物学，小鼠分子遗传学，生物信息学和计算机生物学的专业知识，以获得系统生物学水平的早期哺乳动物面部发育的理解。

Craniofacial morphogenesis is a complex process requiring coordinated proliferation, movement and differentiation of six distinct facial prominences. The complexity of this process leaves it vulnerable to environmental and genetic perturbations, such that craniofacial malformations are one of the most common classes of birth defects. Facial prominences are made up of a mono-layer of ectoderm encasing a large core of neural crest- and mesodermally-derived mesenchymal cells. Signaling from this minor population of ectodermal cells directs and coordinates the behavior of the underlying mesenchyme, and thence facial morphogenesis. Manipulations that alter these signaling processes and tissue interactions have grave consequences for facial development, resulting in various types of medically important dysmorphology including orofacial clefting. Thus a detailed knowledge of geno-dynamics of the ectoderm is an essential component of the overall description of facial development. In this proposal a multi-disciplinary team has been assembled with expertise in craniofacial biology, mouse molecular genetics, bioinformatics and computer biology to gain a Systems Biology level understanding of early mammalian facial development. The ectoderm and the mesenchyme of the wild-type facial prominences will be separated at critical timepoints encompassing facial morphogenesis, then these separated tissues will be used to generate contrasting dynamic spatio-temporal profiles of gene expression and post-translational RNA regulation at the level of splicing, turnover, and translation. These combined studies should provide a valuable resource detailing the dynamic interplay of ectoderm and mesenchyme during normal facial development.