RNA dynamics in the developing mouse face

University Of Colorado Denver, Aurora CO

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Abstract

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.