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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Murphy, Andrew J. Yancopoulos, George D. Hughes, Virginia C. Burfeind, Patricia Wei, Yi Walls, Johnathon R. Lin, Hsin Chieh Daly, Christopher Dominguez, Melissa G. Macdonald, Lynn E. Anderson, Keith D. Simmons, Mary V. Pan, Li Yang, Xiao-man Xue, Yingzi Thurston, Gavin Economides, Aris N. Gale, Nicholas W. Valenzuela, David M. |
| Description | Author Affiliation: Anderson KD ( VelociGene Division, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.); |
| Abstract | The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-ß and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage. We have genetically deleted Gpr124, a member of the large family of long N-terminal group B G protein-coupled receptors, few members of which have identified ligands or well-defined biologic functions in mammals. We show that, in the developing CNS, Gpr124 is specifically expressed in the vasculature and is absolutely required for proper angiogenic sprouting into the developing neural tube. Embryos lacking Gpr124 exhibit vascular defects characterized by delayed vascular penetration, formation of pathological glomeruloid tufts within the CNS, and hemorrhage. In addition, they display defects in palate and lung development, two processes in which TGF-ß and/or Wnt pathways also play important roles. We also show that TGF-ß stimulates Gpr124 expression, and ablation of Gpr124 results in perturbed TGF-ß pathway activation, suggesting roles for Gpr124 in modulating TGF-ß signaling. These results represent a unique function attributed to a long N-terminal group B-type G protein-coupled receptor in a mammalian system. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Central Nervous System Blood Supply Embryology Neovascularization, Physiologic Physiology Receptors, G-Protein-Coupled Metabolism Animals Embryo, Mammalian Genetic Engineering Histological Techniques Immunohistochemistry In Situ Hybridization Lung Mice Microarray Analysis Palate Deficiency Transforming Growth Factor Beta Wnt Proteins Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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