User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse




Journal Article

USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors


Taylor,  Verdon
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Jolly, L. A., Taylor, V., & Wood, S. A. (2009). USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors. Molecular Biology of the Cell, 20, 2015-2029.

Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8F77-6
The substrate-specific deubiquitylating enzyme USP9X is a putative "stemness" gene expressed in many progenitor cell populations. To test its function in embryonic stem cell-derived neural progenitor/stem cells, we expressed USP9X from a Nestin promoter. Elevated USP9X levels resulted in two phenomena. First, it produced a dramatically altered cellular architecture wherein the majority (>80%) of neural progenitors was arranged into radial clusters. These progenitors expressed markers of radial glial cells and were highly polarized with adherens junction proteins (N-cadherin, β-catenin, and AF-6) and apical markers (Prominin1, atypical protein kinase C-ζ) as well as Notch, Numb, and USP9X itself, concentrated at the center. The cluster centers were also devoid of nuclei and so resembled the apical end-feet of radial progenitors in the neural tube. Second, USP9X overexpression caused a fivefold increase in the number of radial progenitors and neurons, in the absence of exogenous growth factors. 5-Bromo-2'-deoxyuridine labeling, as well as the examination of the brain lipid-binding protein: βIII-tubulin ratio, indicated that nestin-USP9X enhanced the self-renewal of radial progenitors but did not block their subsequent differentiation to neurons and astrocytes. nestin-USP9X radial progenitors reformed clusters after passage as single cells, whereas control cells did not, suggesting it aids the establishment of polarity. We propose that USP9X-induced polarization of these neural progenitors results in their radial arrangement, which provides an environment conducive for self-renewal.