Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex

Carlos Oliva,Alessia Soldano,Natalia Mora,Natalie De Geest,Annelies Claeys,Maria-Luise Erfurth,Jimena Sierralta,Ariane Ramaekers,Dan Dascenco,Radoslaw K Ejsmont,Dietmar Schmucker,Natalia Sanchez-Soriano,Bassem A Hassan

doi:10.1016/j.devcel.2016.09.028

Carlos Oliva, Alessia Soldano + Show 11 more

Open Access

https://doi.org/10.1016/j.devcel.2016.09.028

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Abstract

SummaryThe axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body.

Highlights

During nervous system development, proper axon guidance is achieved through the interaction between neuronal cell surface receptors and their chemoattractive or repulsive ligands present in the environment (Chilton, 2006; Dickson and Gilestro, 2006; Lowery and Van Vactor, 2009)
The Drosophila embryonic ventral nerve cord (VNC) has served as a powerful model system for the study of axon guidance by the Slit/Robo pathway (Dickson and Gilestro, 2006) whereby glial cells along the midline express Slit, which acts as a repulsive cue to guide neuronal axons toward or away from the midline in function of their repertoire of Robo receptors
We propose that the mushroom body (MB) acts as a spatially distributed neuronal source of Slit for Drosophila brain connectivity, which could contribute to the higher level of complexity observed in the brain compared with the VNC

Summary

Introduction

Proper axon guidance is achieved through the interaction between neuronal cell surface receptors and their chemoattractive or repulsive ligands present in the environment (Chilton, 2006; Dickson and Gilestro, 2006; Lowery and Van Vactor, 2009). The Drosophila embryonic ventral nerve cord (VNC) has served as a powerful model system for the study of axon guidance by the Slit/Robo pathway (Dickson and Gilestro, 2006) whereby glial cells along the midline express Slit, which acts as a repulsive cue to guide neuronal axons toward or away from the midline in function of their repertoire of Robo receptors This is similar to mammalian spinal cord where a specialized midline structure called the floor plate acts as a major source of guidance cues (Chedotal, 2011). Comm has not been identified in other taxa, suggesting that this mechanism is unlikely to be conserved

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