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RESEARCH PRODUCT

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

Beat LutzMarcus KrügerBenedikt BerningerGuilherme HortaFelipe OrtegaJan BaumgartStefanie KellerPatrick N. HarterTobias BäuerleNevenka Dudvarski StankovicFrank BickerKonstantin RadyushkinMirko H. H. SchmidtLavinia AlberiRui BeneditoHendrik NolteAtria KavyanifarJens HartwigVerica Vasic

subject

Male0301 basic medicineGeneral Physics and AstronomyNEURAL STEM-CELLSMOUSEMiceSUBEPENDYMAL ZONENeural Stem CellsLateral VentriclesLINEAGE PROGRESSIONBRAININ-VIVOMice KnockoutNeuronal PlasticityMultidisciplinaryCell CycleQNeurogenesisNICHEAnatomyNeural stem cellCell biologyAdult Stem Cellsmedicine.anatomical_structureSignal TransductionSTIMULATES NEUROGENESISEGF Family of ProteinsNeurogenesisScienceNotch signaling pathwaySubventricular zoneBiologyInhibitory postsynaptic potentialArticleGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesNeuroplasticitymedicineBiological neural networkAnimalsCalcium-Binding ProteinsProteinsGeneral ChemistryOlfactory PerceptionENDOTHELIAL-CELLSnervous system diseasesOlfactory bulbMice Inbred C57BLSELF-RENEWAL030104 developmental biologynervous system

description

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.

yearjournalcountryeditionlanguage
2016-05-05
10.1038/ncomms15922https://hdl.handle.net/20.500.12105/5110