Cellular mechanisms of lip and palate fusion

 描述(申请人提供)：唇腭裂是常见的先天性畸形，可由组织融合中的缺陷引起，在这个过程中，两个独立的隆起变成一个连续的结构。在发育过程中，组织融合在多种情况下都很常见，包括神经管闭合、心脏和泌尿生殖系统发育，在这些情况下，融合缺陷也会导致结构性出生缺陷。尽管它在发育过程中很重要，但推动组织融合的机械和细胞生成的力量尚不清楚。我们使用新的实时成像方法进行的初步研究揭示了唇腭裂融合背后的动态细胞行为，并引导我们认识到这一过程所需的细胞机械力和力的分子传感器的作用。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推动唇腭裂融合的细胞生成力、机械信号和动态细胞行为。这些研究采用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.