Functional analysis of protein arginine methyltransferase-1 in the mouse embryonic neural stem cells.
Mizuki Honda1, Sayako Katada1, Kinichi Nakashima1
1 Stem cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University

Neural stem cells (NSCs) possess the ability of self-renewal and differentiate into neurons and glial cells such as astrocytes and oligodendrocytes. However, NSCs at mid-gestation only generate neurons, and gradually acquire the potency to differentiate into glial cells in late-gestation. Cell external cues such as cytokine signaling and intracellular epigenetic programs including histone modifications are the two important factors affecting fate determination of NSCs. Arginine methylation is a posttranslational modification catalyzed by the protein arginine methyltransferase (PRMT) family, which are found in both nucleus and cytoplasm. Increasing evidence of arginine methylation of histones and non-histone proteins by PRMTs suggesting that they play roles in the regulation of gene expression and of non-histone protein functions. However, the mechanism of how PRMTs exert effects on NSC regulation is not well understood. Herein, we demonstrate PRMT1 is highly expressed in mouse embryonic NSCs at mid-gestation, and promotes NSC proliferation. Moreover, we found that PRMT1 facilitaes astrocyte differentiation of NSCs by enhancing the expression of astrocyte specific gene, gfap. Finally, we performed in utero electroporation to investigate the function of PRMT1 in vivo. The reduction of PRMT1 by shRNA in the embryonic brain inhibited the migration of newly generated neurons, suggesting that PRMT1 is indispensable for proper radial migration along with neuronal differentiation of NSCs during the development of neocortex. Thus, we report for first time, to the best of our knowledge, that PRMT1 regulates NSC differentiation and neuronal migration.

These works are supported by the Sasakawa Scientific Research Grant from The Japan Science Society.