Regulation of embryonic neurogenesis by germinal zone vasculature

Mathew Tata, Ivan Wall, Andy Joyce, Joaquim M Vieira, Nicoletta Kessaris, Christiana Ruhrberg

Research output: Contribution to journalArticle

Abstract

In the adult rodent brain, new neurons are born in two germinal regions that are associated with blood vessels, and blood vessels and vessel-derived factors are thought to regulate the activity of adult neural stem cells. Recently, it has been proposed that a vascular niche also regulates prenatal neurogenesis. Here we identify the mouse embryo hindbrain as a powerful model to study embryonic neurogenesis and define the relationship between neural progenitor cell (NPC) behavior and vessel growth. Using this model, we show that a subventricular vascular plexus (SVP) extends through a hindbrain germinal zone populated by NPCs whose peak mitotic activity follows a surge in SVP growth. Hindbrains genetically defective in SVP formation owing to constitutive NRP1 loss showed a premature decline in both NPC activity and hindbrain growth downstream of precocious cell cycle exit, premature neuronal differentiation, and abnormal mitosis patterns. Defective regulation of NPC activity was not observed in mice lacking NRP1 expression by NPCs, but instead in mice lacking NRP1 selectively in endothelial cells, yet was independent of vascular roles in hindbrain oxygenation. Therefore, germinal zone vascularization sustains NPC proliferation in the prenatal brain.

Original languageEnglish
Pages (from-to)13414-13419
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number47
Early online date7 Nov 2016
DOIs
Publication statusPublished - 22 Nov 2016

Bibliographical note

© 2016 The Authors

Keywords

  • Animals
  • Blood Vessels/physiology
  • Cell Proliferation
  • Cell Self Renewal
  • Endothelial Cells/metabolism
  • Extracellular Matrix/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitosis
  • Neovascularization, Physiologic
  • Neural Stem Cells/cytology
  • Neurogenesis
  • Neuropilin-1/metabolism
  • Oxygen/metabolism
  • Rhombencephalon/blood supply
  • Time Factors

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