CAREER: Forces Underlying Germ Band Retraction in Drosophila Embryogenesis

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INTELLECTUAL MERITAlthough the body plan of a developing embryo is ultimately determined by its genetic program, the proximate cause of morphogenesis is the generation and regulation of intercellular forces. Genetic approaches to development have been hugely successful, particularly in regard to the genes that determine patterns of cell-fate determination. However, additional genes then determine the mechanical consequences of cell-fate decisions. To unambiguously determine the role of these genes from mutant morphological phenotypes, it is crucial to quantitatively understand the forces underlying morphogenesis. In that spirit, this project involves experimental and computational investigations of the forces underlying the morphogenetic event of germ-band retraction in the fruit fly, Drosophila melanogaster. A working model for germ-band retraction will be experimentally challenged through laser-microsurgery and computational modeling. The working model is based on distinct roles for each of three tissues. These roles are embodied in the following hypotheses: (i) germ-band retraction is driven by spatially and temporally regulated contraction of the amnioserosa; (ii) the germ band itself responds passively to tension in the amnioserosa; and (iii) the distribution of tension in the amnioserosa is determined by contact between the amnioserosa and yolk sac. In light of these hypotheses, the specific goals of this project are:1. To delineate the physical role of the amnioserosa in germ-band retraction (GBR), including the spatial and temporal limitations of this role.2. To determine if there is an active component to the cell shape changes observed in the retracting germ band.3. To quantitatively map and model the forces underlying GBR with high spatial and temporal resolution.4. To link mutant GBR-failure phenotypes to defects in the underlying forces.Note that these goals complement traditional genetic approaches to Drosophila embryogenesis. By focusing on a model organism for which a vast array of genetic techniques are available, the results of this research will provide much-needed leverage, enabling this and future investigations to better connect morphogenesis to the genetic program of development.BROADER IMPACTSIntegral to success in the research goals stated above, the PI's educational plan will enable and encourage students from both physics and biology to work across the disciplinary divide. The four main thrusts of this plan are: (i) to improve the physics education of undergraduate life-science majors by implementing best practices from physics-education research; (ii) to provide interdisciplinary research opportunities for undergraduates; (iii) to recruit under-represented minorities into biophysical research through a partnership with Fisk University, a local HBCU, and (iv) to develop an interdisciplinary graduate course for physical scientists that stresses the ability to communicate complex ideas across disciplinary lines. The major broader impact of these integrated educational activities will be to strengthen interdisciplinary research, both by preparing students to work across the physics/biology interface and by increasing the appreciation of biophysics within the physics and biology mainstreams. Furthermore, the research project provides a new perspective on an exceedingly well-studied system. By defining the mechanical aspects of a major step in Drosophila embryogenesis, this research will build new intellectual infrastructure. It will enable the large community of researchers working on this problem to ask an entirely new set of questions. In addition, the software tools developed in this project (both for image processing and for analyzing the intrinsic forces using laser hole-drilling techniques) will be disseminated broadly to the Drosophila research community.