Motor neurons control blood vessel patterning in the developing spinal cord

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 control...

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Main Authors: Himmels, Patricia (Author) , Paredes Ugarte, Isidora B. (Author) , Adler, Heike (Author) , Karakatsani, Andromachi (Author) , Luck, Robert (Author) , Marti, Hugo (Author) , Ermakova, Olga (Author) , Rempel, Eugen (Author) , Ruiz de Almodóvar, Carmen (Author)
Format: Article (Journal)
Language:English
Published: 2017
In: Nature Communications
Year: 2017, Volume: 8, Pages: 14583
ISSN:2041-1723
DOI:10.1038/ncomms14583
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/ncomms14583
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/ncomms14583
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Author Notes:Patricia Himmels, Isidora Paredes, Heike Adler, Andromachi Karakatsani, Robert Luck, Hugo H. Marti, Olga Ermakova, Eugen Rempel, Esther T. Stoeckli & Carmen Ruiz de Almodóvar

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520 |a 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. 
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