The morphological diversity among neurons is enormous and critical to their function, yet many gaps in our knowledge remain concerning how this diversity is genetically encoded. As with vertebrate motor neurons, the motor neurons of Drosophila melanogaster establish highly specific synapses on the correct muscle fibers in the appendages and also elaborate highly stereotyped dendritic arbors in the central nervous system (CNS). In the previous funding period, we characterized the individual progeny and transcription factor codes that govern neuronal identities for one of the largest neuroblast lineages that give rise to motor neurons and neuropil glia. We further described the role of Ig domain family members in establishing certain aspects of motor neuron identities. Live imaging provided unprecedented access to the relevant stages of motor neuron maturation during pupal stages. In the coming funding period we will extend these findings to understand how transcription factors in post- mitotic neurons regulate their target genes. We will carry out a series of whole genome and single cell studies to obtain this information on a genome-wide scale. Finally, we will analyze additional members of the Ig domain superfamily to assess what other roles, besides axon targeting, they play in motor neuron morphology during development.
Genetic and molecular approaches in the fruit fly, Drosophila melanogaster, will be used to dissect the complex problem of how neurons obtain their unique identities. By focusing on a set of motor neurons used for walking in the adult fly, the goal is to gain insights into how neurons achieve their exquisite synaptic specificities and dendritic architectures, and how perturbations to these morphologies affects coordinated leg movements, such as walking by adult flies.
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