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

Frank Bicker, Verica Vasic, Guilherme Horta, Felipe Ortega, Hendrik Nolte, Atria Kavyanifar, Stefanie Keller, Nevenka Dudvarski Stankovic, Patrick N. Harter, Rui Benedito, Beat Lutz, Tobias Bäuerle, Jens Hartwig, Jan Baumgart, Marcus Krüger, Konstantin Radyushkin, Lavinia Alberi, Benedikt Berninger and Mirko H. H. Schmidt ()
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Frank Bicker: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Verica Vasic: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Guilherme Horta: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Felipe Ortega: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
Hendrik Nolte: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne
Atria Kavyanifar: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Stefanie Keller: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Nevenka Dudvarski Stankovic: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Patrick N. Harter: Edinger-Institute (Neurological Institute), Goethe-University, School of Medicine
Rui Benedito: Molecular Genetics of Angiogenesis Laboratory, Centro Nacional de Investigaciones Cardiovasculares
Beat Lutz: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
Tobias Bäuerle: Preclinical Imaging Platform Erlangen, Institute of Radiology, University Medical Center Erlangen
Jens Hartwig: Institute for Molecular Biology, Johannes Gutenberg University
Jan Baumgart: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Marcus Krüger: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne
Konstantin Radyushkin: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
Lavinia Alberi: Swiss Integrative Center for Human Health SA
Benedikt Berninger: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
Mirko H. H. Schmidt: Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15922

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