Angiogenesis in the mature mouse cortex is governed in a regional- and Notch1-dependent manner
Alejandra Raudales,
Ben Schager,
Dominique Hancock,
Kamal Narayana,
Sorabh Sharma,
Patrick Reeson,
Adam Oshanyk,
Manjinder Cheema,
Jakob Körbelin,
Craig E. Brown
Affiliations
Alejandra Raudales
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Ben Schager
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Dominique Hancock
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Kamal Narayana
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Sorabh Sharma
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Patrick Reeson
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Adam Oshanyk
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Manjinder Cheema
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
Jakob Körbelin
Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
Craig E. Brown
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Corresponding author
Summary: Cerebral angiogenesis is well appreciated in development and after injury, but the extent to which it occurs across cortical regions in normal adult mice and the underlying mechanisms are incompletely understood. Using in vivo imaging, we show that angiogenesis in anterior-medial cortical regions (retrosplenial and sensorimotor cortex) was exceptionally rare. By contrast, angiogenesis was significantly elevated in posterior-lateral regions such as visual cortex, primarily within 200 μm of the cortical surface. There was no effect of sex on angiogenesis rates, nor were there regional differences in vessel pruning (for either sex). To understand the mechanisms, we surveyed gene expression and found that Notch-related genes were enriched in ultra-stable retrosplenial cortex. Using endothelial-specific knockdown of Notch1, cerebral angiogenesis was significantly increased along with genes implicated in angiogenesis (Apln, Angpt2, Cdkn1a). Our study shows that angiogenesis is regionally dependent and that manipulations of Notch1 could unlock the angiogenic potential of the mature vasculature.
