Cell dynamics in calvarial morphogenesis

University Of Texas At Austin, Austin TX

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Abstract

Craniosynostosis is the debilitating precocious ossification of cranial sutures, the fibrous joints between skull bones. 1 in 2500 live births present with synostosis, however, nothing is known about the dynamic cell behaviors underlying calvarial growth and suture formation. Skull defects or damage, such as synostosis or cancer, respectively, are challenging to treat, requiring several reconstructive surgeries. Understanding the morphogenesis of the skull vault may therefore benefit the development of clinical treatment plans and improve faithful skull reconstruction. My recent work shows that the Fuz mutant mouse is a novel model for syndromic craniofacial defects, including craniosynostosis. Here I plan, firstly, to investigate the cause of synostosis in the Fuz mutant using expression, osteogenic and cell mixing analyses. Subsequently, I will utilize a cell biological approach to categorize dynamic cellular behaviors of growing calvarial bones in wildtype and mutant animals. Utilizing fluorescent reporter mouse lines I will perform live imaging analyses of calvarial cells during skull morphogenesis and determine the cell behavior defects underlying craniosynostosis in the Fuz mutant. The Aims proposed here will comprise the first cell biological analysis of skull morphogenesis and will ultimately help determine the necessary modes of cellular behaviors required to drive apical movement of the calvarial bones.