| dc.description.abstract | The vertebrate head is a complex structure consisting of diverse tissues that work cooperatively to perform a variety of craniofacial functions, such as speaking, breathing, processing and swallowing food, among others. Defects in craniofacial morphology can have significant impact on function. Understanding the genetic regulation of both craniofacial form and function during development is currently an understudied aspect of craniofacial biology. Using zebrafish as an in vivo vertebrate model, ERC1, a gene associated with comorbid facial features and neurologic deficits in patients with chromosome 12 microdeletions, was identified as a novel component of a genetic pathway involved in both craniofacial form and function. The kimble/erc1b genetic loss of function mutant exhibited lower jaw movement dysfunction due to cellular defects in jaw muscle organization and innervation by the trigeminal motor nerve. The tissue-specific function of Erc1b in craniofacial muscles and cranial motor nerves was investigated by generation of cell-specific overexpression constructs. Taking advantage of zebrafish genome evolution and reverse genetic techniques, the function of zebrafish paralogous erc1 genes, erc1a and erc1b, were found to be nonredundant during craniofacial development, despite having overlapping tissue expression pattern. Together, this work contributes to the understanding of developmental genetics and pathophysiology of craniofacial abnormalities and dysfunction. | |
