The transcription factor ZEB1 regulates stem cell self-renewal and cell fate in the adult hippocampus
Bhavana Gupta, Adam C. Errington, Ana Jimenez‐Pascual, Vasileios Eftychidis, Simone Brabletz, Marc P. Stemmler, Thomas Brabletz, David Petřík, Florian A. Siebzehnrübl
Abstract
Radial glia-like (RGL) stem cells persist in the adult mammalian hippocampus, where they generate new neurons and astrocytes throughout life. The process of adult neurogenesis is well documented, but cell-autonomous factors regulating neuronal and astroglial differentiation are incompletely understood. Here, we evaluate the functions of the transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) in adult hippocampal RGL cells using a conditional-inducible mouse model. We find that ZEB1 is necessary for self-renewal of active RGL cells. Genetic deletion of Zeb1 causes a shift toward symmetric cell division that consumes the RGL cell and generates pro-neuronal progenies, resulting in an increase of newborn neurons and a decrease of newly generated astrocytes. We identify ZEB1 as positive regulator of the ets-domain transcription factor ETV5 that is critical for asymmetric division.