EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21

The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21contributes to both processes. Accordingly, overexpression of cytoplasmic p21induces NE structural alterations and p21suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation.
This study was supported by grants CSD2006-00049, BFU2009-11527, BFU-2012-34261 to M.A.M.-B. and BFU2009-11527 and BIO2006-15557 to X.C. from the Spanish Ministry of Education and Science, 090210 from Fundaciò La Marató de TV3 and Fondation Jérôme Lejeune to M.A.M.-B. and 200420E578 from the CSIC to X.C. N.A., C.E. and M.A.G. received an I3P fellowship (I3P-BPD2005) and FPU fellowship, respectively