Regulation of embryonic neurogenesis by germinal zone vasculature.
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.
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Mathew
M
Tata
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Ivan
I
Wall
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Andy
A
Joyce
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Joaquim M
JM
Vieira
Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom.
Nicoletta
0000-0003-1191-6009
N
Kessaris
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom; c.ruhrberg@ucl.ac.uk.
Christiana
C
Ruhrberg
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D039942:Neuropilin-1 / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D012249:Rhombencephalon / Q000098:blood supply* / Q000196:embryology*; D013997:Time Factors
D039942:Neuropilin-1; D010100:Oxygen
NRP1; blood vessel; hindbrain; neural progenitor; neurogenesis