Role of Deubiquitylating Enzyme USP9X in Neural Progenitor Fate Determination

Abstract

During brain development, neural progenitors (NPs) need to balance their self-renewal with differentiation, in order to maintain the NP population while establishing the complex tissue architecture of the brain. NP fate is under the close scrutiny of plethora of fate determination factors, which can be divided into two groups based on their site of origin namely, intrinsic and extrinsic fate determinants. To date, a number of intrinsic factors, such as cell polarity and adhesion, and extrinsic factors including Notch, WNT and mTOR signaling pathways have been shown to regulate NP fate specification. Despite a modest understanding of how individual fate determinant pathways influence NP fate, number of significant and fundamental questions remains to be answered; many of which centre on the integration and regulation of distinct determinant factors. The current study focused on understanding how the posttranslational modification, deubiquitylation, contributes to NP fate determination. Conditional deletion of the deubiquitylating enzyme, Usp9x from mouse NPs results in perinatal lethality and diffused cortical cellular architecture during late embryonic stages signifying its importance in NP fate specification (Stegeman et al., 2013). In light of this previous study, the overarching aim of this project was to identify roles, if any, of Usp9x in neural progenitor fate specification.