Morphogenesis Biophysics and Genetics of Dorsal Closure

Duke University, Durham NC

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Abstract

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.