Yale Neurobiologists Discover Surprising Trigger of New Brain Cell Growth

Neural stem cells and nearby blood vessels that express key molecule VEGFR3 are seen in green. VEGFR3 appears to play a role in both formation of new brain cells as well as blood vessels. Credit: Yale University

A newly published study from Yale University shows that adult hippocampal neural stem cells (NSCs) express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells.

Scientists have discovered that the human brain can produce new neurons, but exactly how those cells are produced and what purpose they serve are not well understood. Now a study by Yale researchers shows that key developmental factors that control the formation of blood vessels are also necessary for activating brain stem cells.

Yale neurobiologist Jean-Leon Thomas and colleagues, in collaboration with vascular biologist Anne Eichmann, found that neural stem cells lacking a receptor for vascular endothelial growth factor (VEGFR3) produce fewer new brain cells in the hippocampus of mice. In addition, mice lacking VEGFR3 exhibit more anxiety than mice with intact receptors in stem cells.

Surprisingly, said the researchers, a related VEGF molecule does not stimulate brain blood vessels at doses that activate brain stem cells, which suggests that this factor may be used specifically in the treatment of neurological diseases. The team, including first author Jinah Han, reported their findings February 19 in the journal Cell Reports.

Reference: “Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans” by Jinah Han, Charles-Félix Calvo, Tae Hyuk Kang, Kasey L. Baker, June-Hee Park, Carlos Parras, Marine Levittas, Ulrick Birba, Laurence Pibouin-Fragner, Pascal Fragner, Kaya Bilguvar, Ronald S. Duman, Harri Nurmi, Kari Alitalo, Anne C. Eichmann and Jean-Léon Thomas, 19 February 2015, Cell Reports.
DOI: 10.1016/j.celrep.2015.01.049