Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception

Bicker, Frank; Vasic, Verica; Horta, Guilherme; Ortega, Felipe; Nolte, Hendrik; Kavyanifar, Atria; Keller, Stefanie; Stankovic, Nevenka Dudvarski; Harter, Patrick N.; Benedito, Rui; Lutz, Beat; Baüerle, Tobias; Hartwig, Jens; Baumgart, Jan; Krüger, Marcus; Radyushkin, Konstantin; Alberi, Lavinia; Berninger, Benedikt; Schmidt, Mirko H. H.

doi:10.1038/ncomms15922

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Journal article

Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception

Bicker, Frank Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany
Vasic, Verica Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany
Horta, Guilherme Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Translational Animal Research Center (TARC), Johannes Gutenberg University, Mainz, Germany
Ortega, Felipe Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Institute of Physiological Chemistry, Johannes Gutenberg University, Mainz, Germany - Biochemistry and Molecular Biology Department IV, Faculty of Veterinary Medicine, Complutense University, Madrid, Spain
Nolte, Hendrik Institute for Genetics and CECAD and CMMC, University of Cologne, Germany
Kavyanifar, Atria Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany
Keller, Stefanie Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany
Stankovic, Nevenka Dudvarski Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany
Harter, Patrick N. Edinger-Institute, Goethe-University, Frankfurt am Main, Germany
Benedito, Rui Molecular Genetics of Angiogenesis Laboratory, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
Lutz, Beat Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Institute of Physiological Chemistry, Johannes Gutenberg University, Mainz, Germany
Baüerle, Tobias Preclinical Imaging Platform Erlangen, Institute of Radiology, University Medical Center Erlangen, Germany
Hartwig, Jens Institute for Molecular Biology, Johannes Gutenberg University, Mainz, Germany
Baumgart, Jan Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Translational Animal Research Center (TARC), Johannes Gutenberg University, Mainz, Germany
Krüger, Marcus Institute for Genetics and CECAD and CMMC, University of Cologne, Germany
Radyushkin, Konstantin Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Translational Animal Research Center (TARC), Johannes Gutenberg University, Mainz, Germany
Alberi, Lavinia Swiss Integrative Center for Human Health SA, Fribourg, Switzerland - Unit of Pathology, Department of Medicine, University of Fribourg, Switzerland
Berninger, Benedikt Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany - Institute of Physiological Chemistry, Johannes Gutenberg University, Mainz, Germany
Schmidt, Mirko H. H. Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, Mainz, Germany - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, Mainz, Germany

28.06.2017

Published in:

Nature Communications. - 2017, vol. 8, p. ncomms15922

English Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem cell interface. Fewer inhibitory neurons form in the OB of EGFL7-knockout mice, which increases the absolute signal conducted from the mitral cell layer of the OB but decreases neuronal network synchronicity. Consequently, EGFL7-knockout mice display severe physiological defects in olfactory behaviour and perception.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

Language