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Regulation of tissue growth and morphogenesis.

Animal development is critically dependent upon precisely timed and orchestrated morphogenetic processes including cell shape changes and rearrangements. These morphogenetic events are triggered and controlled by developmentally regulated signaling pathways that lead to cytoskeletal dynamics in individual cells. These forces must then be propagated through the epithelium and maintained in order to elicit appropriate tissue-level morphological changes. These latter steps are dependent on emergent properties of the tissue including the viscosity and elasticity of the epithelium, the stiffness of the membranes and the mechanical properties of the extracellular matrix. An effective way to define novel mechanisms that contribute to these emergent properties is through the characterization of mutations recovered in genetic screens of morphogenesis. Through a series of genetic screens in the fruit fly, Drosophila melanogaster, we have identified a complex of interacting proteins that localize to the lateral membrane as playing critical roles in morphogenetic processes throughout fly development. These proteins ultimately form the septate junction, the primary occluding junction in invertebrate epithelia, however, their role in morphogenesis appears to be independent of this occluding function. Our current projects aim to gain a mechanistic understanding of how these proteins affect adhesion, cytoskeletal dynamics and tissue polarity during morphogenesis at various stages of development including oogenesis, embryogenesis, and metamorphosis.