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Lack of vascular endothelial growth factor receptor-2/Flk1 signaling does not affect substantia nigra development

Hermann, Andreas and Loewenbrück, Kai F. and Boldt, Änne and Fiedler, Christiane and Maisel, Martina and Kalucka, Joanna and Schwarz, Johannes and Breier, Georg and Storch, Alexander (2013) Lack of vascular endothelial growth factor receptor-2/Flk1 signaling does not affect substantia nigra development. Neuroscience Letters, 553 . pp. 142-147. ISSN 0304-3940.

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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.

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Additional Information:© 2013 Elsevier Ireland Ltd. Received 13 June 2013. Received in revised form 29 July 2013. Accepted 11 August 2013. We acknowledge Sylvia Kanzler, Silvia Krakau, Cornelia Mai,Rosi Mueller, Antje Muschter for excellent technical assistance and Grit Weselek for fruitful discussions. The work was supported in part by the Deutsche Parkinson-Gesellschaft (DPG) to A.H., by a GlaxoSmithKline fellowship to A.H., by the Deutsche Forschungsgemeinschaft (DFG) through the DFG-Research Center for Regenerative Therapies Dresden (CRTD) to A.H. and A.S. and though the SFB 655 to A.S. and G.B. The authors report no conflict of interest.
Funding AgencyGrant Number
Deutsche Parkinson-Gesellschaft (DPG)UNSPECIFIED
GlaxoSmithKline fellowshipUNSPECIFIED
DFG-Research Center for Regenerative Therapies Dresden (CRTD)UNSPECIFIED
Subject Keywords: Midbrain neurogenesis; Hypoxia; HIF1α signaling; Flk1 signaling
Record Number:CaltechAUTHORS:20131121-142429534
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Official Citation:Andreas Hermann, Kai F. Loewenbrück, Änne Boldt, Christiane Fiedler, Martina Maisel, Joanna Kalucka, Johannes Schwarz, Georg Breier, Alexander Storch, Lack of vascular endothelial growth factor receptor-2/Flk1 signaling does not affect substantia nigra development, Neuroscience Letters, Volume 553, 11 October 2013, Pages 142-147, ISSN 0304-3940, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42629
Deposited By: Ruth Sustaita
Deposited On:21 Nov 2013 22:52
Last Modified:03 Oct 2019 06:00

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