Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling
Marlen Zschätzsch,
Carlos Oliva,
Marion Langen,
Natalie De Geest,
Mehmet Neset Özel,
W Ryan Williamson,
William C Lemon,
Alessia Soldano,
Sebastian Munck,
P Robin Hiesinger,
Natalia Sanchez-Soriano,
Bassem A Hassan
Affiliations
Marlen Zschätzsch
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven Group Biomedicine, Leuven, Belgium
Carlos Oliva
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Marion Langen
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Program in Molecular and Cognitive Neuroscience, Doctoral School for Biomedical Sciences, University of Leuven Group Biomedicine, Leuven, Belgium
Natalie De Geest
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Mehmet Neset Özel
Department of Physiology and Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, United States
W Ryan Williamson
Department of Physiology and Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, United States
William C Lemon
Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
Alessia Soldano
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium
Sebastian Munck
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Bio Imaging Core, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
P Robin Hiesinger
Department of Physiology and Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, United States
Natalia Sanchez-Soriano
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Bassem A Hassan
Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium; Center of Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven Group Biomedicine, Leuven, Belgium; Program in Molecular and Cognitive Neuroscience, Doctoral School for Biomedical Sciences, University of Leuven Group Biomedicine, Leuven, Belgium; Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors.
