title: Motor neurons control blood vessel patterning in the developing spinal cord.
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.
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Himmels
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Isidora
authors.initials: I
authors.lastname: Paredes
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Adler
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Andromachi
authors.initials: A
authors.lastname: Karakatsani
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Luck
authors.affiliation: Institute of Physiology and Pathophysiology, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Marti
authors.affiliation: Department of Stem Cell Biology, Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Ermakova
authors.affiliation: Department of Stem Cell Biology, Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Rempel
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Esther T
authors.initials: ET
authors.lastname: Stoeckli
authors.affiliation: Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.|Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz de Almodóvar
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001808:Blood Vessels / Q000254:growth & development / Q000378:metabolism*; D019521:Body Patterning / Q000235:genetics; D002645:Chickens; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; C467480:vascular endothelial growth factor A, mouse; D039942:Neuropilin-1; D049452:Green Fluorescent Proteins; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1