First Author | Gomez HG | Year | 2019 |
Journal | Biol Open | Volume | 8 |
Issue | 6 | PubMed ID | 31142467 |
Mgi Jnum | J:275629 | Mgi Id | MGI:6307719 |
Doi | 10.1242/bio.039248 | Citation | Gomez HG, et al. (2019) Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism. Biol Open :bio039248 |
abstractText | The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (SUFU) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B1 cells. In contrast, we found a significant decrease in Gsx2+ and a more dramatic decrease in Tbr2+ transit amplifying cells (TACs) indicating that innate differences between dorsal and ventral forebrain derived Type B1 cells influence Sufu function. However, many precursors accumulated in the dorsal V-SVZ or failed to survive, demonstrating that despite the over-proliferation of Type B1 cells, they are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression and surprisingly, a significant downregulation of Sonic hedgehog (Shh) signaling. Therefore, these findings indicate a potential role of the Sufu-Gli3 regulatory axis in the neonatal dorsal V-SVZ independent of Shh signaling in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ. |