Genetics of neural precursor communication during development of the Drosophila peripheral nervous system

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Genetics of neural precursor communication during development of the Drosophila peripheral nervous system The long-term goal of this research is to understand how cell-cell signaling mechanisms drive the organization of the developing peripheral nervous system (PNS). The incorrect spatial and temporal induction of genes and cell behaviors by perturbed signaling can lead to catastrophic errors in an organism’s ability to sense and respond to environmental stimuli. A model system for studying PNS development is the patterning of mechanosensory bristles on the dorsal thorax of the fruit fly Drosophila melanogaster. The developing thoracic PNS undergoes pattern refinement, or the improvement of an initally disordered pattern with time. At least three behaviors of neural precursor cells contribute to pattern refinement, including cell fate switching, adjusting the timing of cell cycle progression, and programmed cell death. The behavioral outcomes that contribute to pattern refinement rely on communication between neural precursor cells, although the mechanisms by which the cells communicate are not known. In Aim 1, a targeted RNAi screen will be performed to test for genes involved in precursor cell communication. The use of Drosophila genetics, adult behavioral assays, and quantitative microscopy will identify candidate genes whose knockdown leads to changes in the pattern refinement process. In Aim 2, an ex vivo strategy will be developed in order to manipulate neural precursor interactions. This novel approach using synthetic 3D scaffolds will test the hypothesis that signaling filopodia (cytoneme) mediated contact is required for neural precursor communication during pattern refinement. Altogether, the innovation of the proposed research lies in its dual approach of identifying both genetic and physical requirements of neural precursor cell-cell communication during pattern refinement. The proposed work is significant because it is expected to uncover conserved mechanisms of cell-cell communication that can be used to target, manipulate, and study neurogenesis and patterning across model systems.