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

Author

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  • Frank Bicker

    (Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine)

  • Verica Vasic

    (Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine)

  • Guilherme Horta

    (Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
    Translational Animal Research Center (TARC), Johannes Gutenberg University, School of Medicine)

  • Felipe Ortega

    (Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
    Institute of Physiological Chemistry, Johannes Gutenberg University, School of Medicine
    Faculty of Veterinary Medicine, Complutense University)

  • 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
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine)

  • Stefanie Keller

    (Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University, School of Medicine
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), 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
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), 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
    Institute of Physiological Chemistry, 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
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
    Translational Animal Research Center (TARC), 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
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
    Translational Animal Research Center (TARC), Johannes Gutenberg University, School of Medicine)

  • Lavinia Alberi

    (Swiss Integrative Center for Human Health SA
    Unit of Pathology, University of Fribourg)

  • Benedikt Berninger

    (Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine
    Institute of Physiological Chemistry, 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
    Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine)

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.

Suggested Citation

  • 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, 2017. "Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15922
    DOI: 10.1038/ncomms15922
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