The organization of dendritic arbors dictates how effectively a neuron can respond to extracellular signals. Although many factors have been identified that are essential for establishing dendritic morphology during development, much less is known about how the branching patterns are subsequently refined and maintained. The well-characterized dendritic arborization (da) neurons in the Drosophila larva have been fundamental in identifying genes that are important for dendrite morphogenesis. Nanos (Nos) and Pumilio (Pum), which were first identified as part of a translational repression complex in the Drosophila embryo, are required to maintain dendritic arborization in the highly branched class IV da neurons.
We aim to identify the downstream targets of Nos and Pum function that are essential for dendrite morphogenesis. Recent genetic analyses from our lab suggest that the defects in dendritic arborization observed in nos- and pum-deficient larvae arise partially from an increase in expression of the pro-apoptotic factor Head involution defective (Hid). Nonapoptotic functions of caspase activity, mediated through members of the apoptotic pathway, are important for many developmental processes, including pruning and dendrite remodeling of class IV da neurons during metamorphosis. We propose biochemical and genetic analyses to test the hypothesis that the Nos/Pum complex modulates nonapoptotic caspase function through regulation of hid in order to maintain dendritic complexity in larval class IV da neurons prior to metamorphosis. In addition, a genetic suppression screen will enable us to identify other downstream targets of Nos/Pum that are required for dendrite morphogenesis.
Defects in neuronal morphogenesis can lead to a number of neurological disorders;therefore, characterizing the mechanisms of gene regulation that lead to proper neuronal development can give insight into the pathways that are essential for nervous system function and integrity. This training proposal will focus on characterizing post-transcriptional regulatory mechanisms that are important for dendritic arborization and will give us a better understanding of how regulation of certain pathways and/or factors impinge on normal neuronal development.
|Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R (2016) Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals. Development 143:2147-59|