Morphogenesis Biophysics and Genetics of Dorsal Closure

描述（由申请人提供）：对果蝇背侧闭合的定量分析表明，这种模型细胞片的运动取决于三个不同的生物过程（ms . Hutson et al . 2003 Science 300:145及其中的参考文献）。这三个过程包括：位于外侧表皮前缘的细胞上钱包串的收缩性；羊膜的收缩性；和Celt薄片拉链，在本机关闭保持曲率，并允许钱包线保持曲率和贡献力-有利于关闭。第四个过程在外侧和腹侧表皮产生张力，反对闭合。背侧闭合是坚固和有弹性的：促进闭合的单个力远远超过净力，即使在通常起作用的一种力消除后，施加的力和闭合仍以接近自然的速度进行。在这里，我们专注于应用我们开发的激光手术和定量建模工具，以便更详细地探索该模型系统中细胞片形态发生的细胞和分子机制。通过将这些方法应用于未能完全关闭的突变体（所谓的DC基因突变）的分析，我们验证了以下假设。非肌球蛋白II为细胞上的荷包线、羊膜和外侧表皮提供收缩力。定量分析将揭示其他DC基因如何参与这一过程。这种压缩需要同源基因参与脊椎动物的黏附和黏附连接形成。最后，导致背侧闭合的力的相对平衡是通过机械门控通道和/或局灶粘连或连接复合物组分的功能来调节的。我们推测，这些关于果蝇细胞片形态发生的研究将为脊椎动物形态发生和伤口愈合中协调细胞形状变化的生物学过程提供细胞和分子基础。

DESCRIPTION (provided by applicant): Quantitative analysis of dorsal closure in Drosophila establishes that this model cell sheet movement depends on the contribution of three distinct biological processes (M.S. Hutson et al 2003 Science 300:145 and references therein). The three processes include contractility in a supra-cellular purse-string at the leading edge of the lateral epidermis; contractility of the amnioserosa; and celt sheet zipping, which in native closure maintains curvature and allows the purse string to maintain curvature and contribute force - favor closure. A fourth process produces tension in the lateral and ventral epidermis that opposes closure. Dorsal closure is robust and resilient: the individual forces that contribute to closure are far in excess of the net, applied force and closure proceeds at near native rates even after the removal of one of the forces that usually contributes. Here we focus on applying the laser-surgical and quantitative-modeling tools that we have developed in order to explore in greater detail the cellular and molecular mechanisms of cell sheet morphogenesis in this model system. By applying these methods to the analysis of mutants that fail to complete closure (mutations in so-called DC genes), we test the following hypotheses. That nonmuscle myosin II provides contractile force for the supra-cellular purse-string, the amnioserosa and the lateral epidermis. That quantitative analysis will reveal how other DC genes contribute to the process. That zipping requires genes whose homologs contribute to focal adhesion and adherens junction formation in vertebrates. And finally, that the relative balances of forces that contribute to dorsal closure are regulated through the function of mechanically gated channels and/or components of focal adhesions or junctional complexes. We speculate that these studies on cell sheet morphogenesis in Drosophila will provide insight into the cellular and molecular basis for the biological processes that coordinate cell shape changes in vertebrate morphogenesis and wound healing.