The research plan will refine and deploy a set of advanced tools for the imaging of tissue structure, gene expression domains and cellular dynamics during craniofacial development. Volumetric imaging tools will be used td create accurate 3D atlases that can be digitally dissected to permit the tissue interactions and cellular events to be better understood in the forming faces of normal, mutant and perturbed mouse and avian embryos. Molecular imaging agents, optimized for imaging intact tissues, will be employed to create atlases of the molecular correlates of these embryos. Finally, intraviral imaging tools will be used to study cell and tissue interactions as they take place, offering a view into the dynamic events that execute craniofacial development. The data will be assembled into atlases that will offer unprecedented tools for exploring the cellular, tissue and molecular correlates of craniofacial development. These atlases will be made widely available for the use of others in the Face Base consortium and the broader community of craniofacial researchers through an online resource created locally. In addition, they will be linked to other Face Base resources through established hubs, so that the data in our atlases can be used in concert with the molecular and structural data provided by other members of the consortium. The data acquisition pipeline established here in close collaboration with the laboratories of Dr. Yang Chai (University of Southern California) and Dr. Marianne Bronner-Fraser (Caltech) will create a model that can be expanded to phenotype and analyze other experimental systems.
Cleft palate, with or without cleft lip. is one of the more common birth defects, affecting approximately one in 2500 live births. The basic events by which cells of different origin come together to form the face have long been known, but the exact tissue movements and the signals that guide them remain undefined. The goal of this work is to help fill this void by imaging the morphology of normal craniofacial development, the abnormal development seen in cleft palate, and providing a means to experimentally test the roles of signaling pathways in the tissue interactions that build the face. This work offers a powerful platform for devising and testing potential therapeutic approaches.
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