Cleft lip and palate are common congenital anomalies that can arise from defects in tissue fusion, a process in which two independent prominences become one continuous structure. Tissue fusion is common across multiple contexts during development, including neural tube closure, heart, and urogenital development, and defects in fusion also lead to structural birth defects in these contexts. Despite its importance during development, the mechanical and cell-generated forces that drive tissue fusion are not understood. Our preliminary studies using novel live imaging methodologies reveal dynamic cell behaviors underlying lip and palate fusion and lead us to appreciate the role of cellular mechanical forces and molecular sensors of force required for this process. We will utilize mouse genetics, physical manipulation, and confocal live imaging to define the cell-generated forces, mechanical signaling and dynamic cell behaviors driving lip and palate fusion. These studies take a new approach to understanding tissue fusion during development and will shed light on longstanding questions in the field, leading to improved understanding of structural birth defects that involve tissue fusion.
Cleft lip and palate are common and devastating birth defects that can arise from a failure of tissue fusion during development, a process involving the integration of two separate embryonic primordia into a single continuous structure. Nevertheless, our understanding of tissue fusion is incomplete with a particular gap in knowledge of the mechanical forces and cellular dynamics that drive this event. We propose to test a new model for tissue fusion wherein cell-generated forces drive multiple cell behaviors to facilitate fusion of the upper lip and secondary palate.
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|Kim, Seungil; Prochazka, Jan; Bush, Jeffrey O (2017) Live Imaging of Mouse Secondary Palate Fusion. J Vis Exp :|