title: Lack of vascular endothelial growth factor receptor-2/Flk1 signaling does not affect substantia nigra development.
abstract: Oxygen tension is critical for proliferation of human and murine midbrain-derived neural precursor cells (mNPCs). Lack of hypoxia-inducible factor-1α (HIF1α) impairs midbrain dopaminergic neurogenesis which could be rescued by vascular endothelial growth factor (VEGF) via VEGFR-2 signaling. Here, we conditionally inactivated the VEGFR-2, encoded by the fetal liver kinase 1 (Flk1) gene, in murine NPCs to determine its role in proliferation and survival in vitro as well as survival of dopaminergic neurons in vivo. Flk1 conditional knock-out (Flk1 CKO) mice showed no general brain phenotype. There was no midbrain-specific impairment of NPC proliferation as seen in HIF1α CKO mice. In the substantia nigra (SN) of adult Flk1 CKO mice, nonbiased stereological cell counts revealed no reduction of TH-positive neurons of Flk1 CKO mice compared with control Cre/wt mice (in which the wild-type Flk1 allele is expressed in parallel with the Cre recombinase allele). In conclusion, VEGF receptor signaling seems not to be relevant to the development and survival of substantia nigra dopaminergic neurons within the hypoxia-HIF1α signaling pathway.
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, Dresden University of Technology, Dresden, Germany; Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Centre for Neurodegenerative Diseases (DZNE) Dresden, Dresden University of Technology, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.forename: Kai F
authors.initials: KF
authors.lastname: Loewenbrück
authors.forename: Änne
authors.initials: Ä
authors.lastname: Boldt
authors.forename: Christiane
authors.initials: C
authors.lastname: Fiedler
authors.forename: Martina
authors.initials: M
authors.lastname: Maisel
authors.forename: Joanna
authors.initials: J
authors.lastname: Kalucka
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwarz
authors.forename: Georg
authors.initials: G
authors.lastname: Breier
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
mesh_terms: D000818:Animals; D002470:Cell Survival; D059290:Dopaminergic Neurons / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D015398:Signal Transduction; D013378:Substantia Nigra / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Flk1 signaling; HIF1α signaling; Hypoxia; Midbrain neurogenesis