Cellular mechanisms of lip and palate fusion

 描述（由申请人提供）：唇腭裂是常见的先天性异常，可能由组织融合缺陷引起，组织融合是两个独立的组织融合成一个连续结构的过程。组织融合在发育过程中的多种情况下是常见的，包括神经管闭合、心脏和泌尿生殖系统发育，并且融合缺陷也会导致这些情况下的结构性出生缺陷。尽管它在发育过程中很重要，但驱动组织融合的机械力和细胞产生的力尚不清楚。我们的初步研究使用新的活成像方法揭示了唇腭融合的动态细胞行为，并使我们认识到这一过程所需的细胞机械力和分子传感器的作用。我们将利用小鼠遗传学、物理操作和共聚焦实时成像来定义驱动唇和腭融合的细胞产生的力、机械信号和动态细胞行为。这些研究采取了一种新的方法来理解发育过程中的组织融合，并将阐明该领域长期存在的问题，从而提高对涉及组织融合的结构性出生缺陷的理解。

 DESCRIPTION (provided by applicant): 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.