The Fly “Dpr-ome” in nervous system development and synaptic connectivity

Carillo

Robert Carillo

(Cal Tech)

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Date: February 17, 2016

Description:

The development of neural circuits requires a highly regulated series of steps culminating in the precise connectivity seen in the mature circuit. One mechanism proposed by Roger Sperry and others hypothesized that synaptic partners express a complementary set of cell surface proteins (CSPs) which allows for their specific interaction. We have defined a network of interacting Drosophila CSPs, the “Dpr-ome”, in which a 21-member IgSF subfamily, the Dprs, binds to a 9-member subfamily, the DIPs (in collaboration with Christopher Garcia’s lab at Stanford and Hugo Bellen’s group at Baylor). Preliminary studies of 18 of the 30 genes in the Dpr-DIP subfamilies shows that they are expressed in small and unique subsets of neurons in the Drosophila nervous system supporting the idea of neuronal surface labels in controlling connectivity. We focused on one of these interacting pairs: Dpr11 and DIP-γ. In the larval neuromuscular system, Dpr11 and DIP-γ are expressed pre- and postsynaptically and required for proper development of the presynaptic terminal. dpr11 and DIP-γ mutants also show an impairment in spontaneous neurotransmission and genetic interaction experiments reveal a role in modulating BMP signaling. In the visual system, dpr11 is selectively expressed by a subtype of R7 photoreceptors. Their primary synaptic targets, Dm8 amacrine neurons, express DIP-γ. In dpr11 or DIP-γ mutants, the terminals of these R7 photoreceptors extend beyond their normal termination zones in the medulla. In addition, survival of Dm8 neurons is dependent on DIP-γ. Recent data focused on a different hub of the Dpr-ome suggests that other members function in motor neuron target selection. Our findings suggest that Dpr-DIP interactions are important determinants of synaptic development and circuit formation.

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Created: Wednesday, February 17th, 2016