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Dev Cell. 2016 Oct 24;39(2):267-278. doi: 10.1016/j.devcel.2016.09.028.

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

Author information

1
Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Physiology and Biophysics Department, Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile.
2
Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
3
Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Neuronal Wiring Laboratory, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Institute of Biochemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
4
Physiology and Biophysics Department, Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile.
5
Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Neuronal Wiring Laboratory, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium.
6
Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, 75013 Paris, France.
7
Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
8
Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, 75013 Paris, France. Electronic address: bassem.hassan@icm-institute.org.

Abstract

The 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.

KEYWORDS:

Drosophila; axon growth; axon guidance; brain wiring; mushroom body; neural circuit development; receptor protein tyrosine phosphatase; robo; slit

PMID:
27780041
PMCID:
PMC5084709
DOI:
10.1016/j.devcel.2016.09.028
[Indexed for MEDLINE]
Free PMC Article

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