Dynamics of epithelial morphogenesis

描述：我们建议结合计算和实验方法来研究上皮形态发生的机制，上皮形态发生的定义是将细胞片状转化为组织和器官的三维(3D)结构的一组过程。上皮形态发生的研究对于了解正常发育和阐明发育异常的起源，如神经管缺陷具有重要意义。我们将专注于一种只涉及细胞形状变化和重排的上皮形态发生，而不依赖于细胞分裂或死亡。这种形态发生的例子包括鱼类心脏发育的早期阶段，鸟类视杯的形成，以及昆虫的中胚层内陷。在我们的实验系统(果蝇卵子发生)中，一片未分裂的细胞形成了一个精心制作的3D形状。这种转变是由众所周知的化学信号诱导的，这些信号指定了命运图，即细胞在薄片内的位置与它们在3D结构中的最终位置之间的对应关系。我们的目标是了解二维(2D)命运地图是如何转化为3D结构的。回答这个问题在从简单的后生动物到人类的多种发育系统中都很重要。我们的假设是，果蝇卵子发生过程中的3D上皮形态发生是由花纹细胞板内机械张力的2D分布驱动的。我们将通过对上皮细胞动力学的计算建模和实时成像，以及通过直接分析有图案的上皮片中的机械张力来检验这一假设。我们的工作将导致一个经过实验验证的三维上皮形态发生的计算框架。考虑到参与上皮形态发生的过程的高度保守性，这些结果或研究可能有助于揭示广泛发育系统中的上皮动力学。

DESCRIPTION: We propose to combine computational and experimental approaches to investigate the mechanisms of epithelial morphogenesis, defined as the set of processes that transform sheets of cells into three-dimensional (3d) structures of tissues and organs. Studies of epithelial morphogenesis are important for understanding of normal development and for elucidating the origins of developmental abnormalities, such as neural tube defects. We will focus on a type of epithelial morphogenesis that involves only cell shape changes and rearrangements and does not depend on cell divisions or death. Among the examples of this type of morphogenesis are the early stages of heart development in fish, the formation of optic cups in birds, and mesoderm invagination in insects. In our experimental system (Drosophila oogenesis), a sheet of nondividing cells gives rise to an elaborate 3d shape. This transformation is induced by well-understood chemical signals, which specify a fate map, a correspondence between positions of cells within the sheet and their ultimate positions within the 3d structure. Our goal is to understand how the two-dimensional (2d) fate map is transformed into a 3d structure. Answering this question is important in multiple developmental systems, from simple metazoans to humans. Our hypothesis is that 3d epithelial morphogenesis during Drosophila oogenesis is driven by the 2d distribution of mechanical tensions within the patterned cell sheet. We will test this hypothesis by computational modeling and live imaging of epithelial dynamics and by direct analysis of mechanical tensions in patterned epithelial sheets. Our work will lead to an experimentally validated computational framework for 3d epithelial morphogenesis. Given the highly conserved nature of processes involved in epithelial morphogenesis, the results of or studies may shed light on epithelial dynamics in wide range of developmental systems.