Oligodendrocyte Development and Regeneration

In the postnatal and adult brain, OPCs arise from radial glial cells (RGCs) of the subventricular zone (SVZ), a major gliogenic and neurogenic region of the brain. OPC proliferate in the SVZ and migrate throughout the brain to gray and WM, where they mature into myelinating OLs. While some important signaling pathways have been characterized, much remains unknown about homeostatic regulation of OPC proliferation and maturation in the SVZ, both during normal development and after injury. Furthermore, although it is established that the proliferative response of endogenous OPCs to injury is crucial for expanding this progenitor pool and for regenerating a normal number of OLs, the endogenous molecular signals involved in the regulation of OPC proliferation in the SVZ are still largely undefined. We utilized our previously generated Endothelin-1 (ET-1) and ET-1 receptor (Ednr) mouse mutant lines and discovered that in the postnatal brain, RGC-derived ET-1 plays a novel and different role, i.e., regulates OPC proliferation. We are now testing the hypothesis that ET-1 signaling between RGCs and OPCs plays a crucial role in SVZ developmental homeostasis and regeneration.

Subventricular zone. The image above is of the dorsal subventricular zone in a young mouse (postnatal day 18) showing expression of Endothelin-1 (green), Glial fibrillary acidic protein (GFAP, red) and cell nuclei (DAPI, blue). GFAP+ astrocytes express the Endothelin-1 protein.