+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system

Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system

Developmental Dynamics 231(3): 503-509

Recent evidence indicates that sprouting angiogenesis in the central nervous system (CNS) is a guided process similar to the guidance of axons and insect tracheal tubes. Specialized tip cells of vessel sprouts navigate in response to local depots or gradients of vascular endothelial growth factor (VEGF-A). Neuropilin-1 (Nrp-1) is a transmembrane receptor with a repulsive function in axon guidance. Nrp-1 also binds the VEGF-A splice isoform VEGF165, stimulates angiogenesis, and is necessary for vascular development in the mouse. However, the morphogenetic events controlled by Nrp-1 in angiogenesis have not been defined. Here, we analyzed endothelial tip cell guidance in the CNS of Nrp-1-deficient mice. We focused our attention on the developing hindbrain, which is normally vascularized in a stereotyped manner. Initially, angiogenic sprouts extend along radial glia from the pial surface toward the ventricles, but in the subventricular zone (SVZ), they leave the radial path, turn laterally, and fuse to form a capillary plexus. Radial sprout elongation correlated with tip cell filopodia extensions along nestin-positive radial glial processes, but in the SVZ, the tip cell filopodia also extended perpendicular to the glial tracks and made contact with filopodia of the neighboring sprouts. In Nrp-1-deficient mice, the tip cell filopodia remained associated with the radial glia in the SVZ, which correlated with a failure of sprout turning and elongation across this region. As a result, the sprouts remained blind-ended forming glomeruloid tufts in the SVZ. These observations suggest that Nrp-1 plays an important role in allowing the endothelial tip cell filopodia to switch substrate and protrude in a new direction at a specific location in the developing brain.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 012349433

Download citation: RISBibTeXText

PMID: 15376331

DOI: 10.1002/dvdy.20148

Related references

Cell patterning and axon guidance in the developing vertebrate central nervous system. Journal of Cellular Biochemistry Supplement (13 PART C): 242, 1989

Vascular Endothelial Growth Factor receptor neuropilin-1 in primary neoplasms of the central nervous system. Brain Pathology 10(4): 735, September, 2000

Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Developmental Biology 170(1): 207-222, 1995

Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell. 87(6): 1001-1014, 1996

Growth-associated protein-43 is required for commissural axon guidance in the developing vertebrate nervous system. Journal of Neuroscience 22(1): 239-247, 2002

MAP1B is required for axon guidance and Is involved in the development of the central and peripheral nervous system. Journal of Cell Biology 151(6): 1169-1178, 2000

Guidance of longitudinally projecting axons in the developing central nervous system. Frontiers in Molecular Neuroscience 5: 59, 2012

Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Developmental Brain Research. 84(1): 109-129, 1995

Neuropilin is an essential cell surface molecule in PNS axons guidance A study in neuropilin-deficient mice. Neuroscience Research Supplement 0(21): S120, 1997

Growth cone guidance by glial and neuronal surfaces in the developing central nervous system of the drosophila embryo an ultrastructural study. Society for Neuroscience Abstracts 12(1): 195, 1986

Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish. Plos One 8(5): E63757, 2013

Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival. Embo Journal 13(12): 2876-2885, 1994

A tumor necrosis factor receptor 1-dependent conversation between central nervous system-specific T cells and the central nervous system is required for inflammatory infiltration of the spinal cord. American Journal of Pathology 168(4): 1200-1209, 2006

The midline of the Drosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance. Cell 64(4): 801-815, 1991