HDAC3 Mediates Visual Experience-Dependent Radial Glia Proliferation In The Xenopus Tectum

Radial glial cells(RGs)are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system(CNS).Histone deacetylases(HDACs)has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain.However,it is unclear whether two other members of class I HDACs,HDAC2 and HDAC3,are involved in the regulation of radial glia proliferation.Radial glial cells(RGs)have been shown as one of the major forms of progenitor cells in Xenopus laevis.Here,we found that HDAC2 and HDAC3 expression were developmentally regulated in tectal cells,especially in the ventricular layer of the BLBP-positive RGs.We using an inhibitor of class I HDACs,MS-275,decreased the number of BrdU-positive dividing progenitor cells.We had shown that HDAC1 is involved in the experience-dependent proliferation of RGs.Therefore,we specific knockdown of HDAC3 but not HDAC2 decreased the number of BrdU-and BLBP-labeled cells,suggesting that the proliferation of radial glia was selectively mediated by HDAC3.Furthermore,we also found that visual deprivation induced selective augmentation of histone H4 acetylation at lysine 16 in BLBP-positive cells.In addition,the visual deprivation-induced increase in BrdU-positive cells was partially blocked by HDAC3 downregulation but not by HDAC2 knockdown at stage 49 tadpoles.Our data clearly provide evidence that BLBP-positive RG cells are SOX2-positive progenitor cells.HDAC3 but not HDAC2 selectively down regulates BrdU-positive RGs in the ventricular layer of the tectum.Moreover,HDAC3 blocks visual deprivation-induced increase of BrdU-positive progenitor cells.It will be important for the further studies to address the downstream signaling that control the differentiation and proliferation of radial glia for brain repair and formation.