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.
