Integration of orthogonal patterning information is necessary for regulating form during Drosophila body axis elongation: Towards an understanding of how genetic fate controls embryonic shape

Princeton University, Princeton NJ

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Abstract

Project Summary Successful development of metazoan embryos requires that a complex series of cell movements and differentiation events be carried out in three dimensions. In Drosophila?one of the best-understood systems for developmental studies? signals for development, called morphogens, are arranged along the anterior/posterior axis (AP) in the form of three transcription factors, Bicoid, Nanos, and Torso. A single major morphogen for signaling along the dorsal/ventral (DV) axis is the nf/Kb transcription factor Dorsal. One critical way in which the embryo must respond to these signals is by organizing its myosin contractile machinery to generate the forces needed to power the coordinated movement of sheets of cells in the proper places at the proper times. During germ band extension, the process of body axis elongation in Drosophila, a highly coordinated pattern of intercalary behavior among cells within the germ band tissue leads to a dramatic 2 fold elongation of body axis length. Until recently the assembly of the actomyosin contractile apparatus responsible for cell intercalation in this process was thought to be controlled solely by AP patterning signals. Preliminary data upon which this proposal is based describes an unexpected gradient of force caused by myosin contractility that develops along the germ band tissue. This suggests that the DV axis also controls the regulation of the actomyosin contractile machinery in the germ band. Experiments in this proposal will utilize the power of a newly developed global imaging modality to test two non-mutually exclusive hypotheses. The first is that the DV patterning system modulates AP patterning cues directly. The second is that the regulatory target of the DV patterning system is the contractile machinery itself. The answer to these questions, given conserved nature of integration of patterning information from orthogonal axes for controlling coordinated cell movement in metazoans, should provide important new insights into mammalian development and potential disease etiology.