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Nat Commun. 2017 Mar 6;8:14583. doi: 10.1038/ncomms14583.

Motor neurons control blood vessel patterning in the developing spinal cord.

Author information

1
Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.
2
Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
3
Institute of Physiology and Pathophysiology, Heidelberg University, 69120 Heidelberg, Germany.
4
Department of Stem Cell Biology, Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
5
Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.

Abstract

Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF). We describe that motor neurons express the VEGF trapping receptor sFlt1 via a Neuropilin-1-dependent mechanism. Using a VEGF gain-of-function approach in mice and a motor neuron-specific sFlt1 loss-of-function approach in chicken, we show that motor neurons control blood vessel patterning by an autocrine mechanism that titrates motor neuron-derived VEGF via their own expression of sFlt1.

PMID:
28262664
PMCID:
PMC5343469
DOI:
10.1038/ncomms14583
[Indexed for MEDLINE]
Free PMC Article

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