DNA methylation and cerebellar development, the regulation of Notch and Shh pathway

Abstract

Our purpose is to elucidate the roles of some molecules and DNA methylation in cerebellar development. Immunocytochemistry was performed to investigate the expression of activated Notch1 and Sonic Hedgehog (Shh), as well as DNA methylation during cerebellar development at various ages. Notch1 could be expressed in neural stem cells, newborn neurons and Purkinje cells during cerebellar development. However, Shh could be expressed mainly in developing radial glia or Bergmann cells specifically. DNA methylation was present during cerebellar development, mainly in neural progenitor cells and developing granule cells. The formation and maturation of both Purkinje cells and Bergmann cells are required for the differentiation and migration of granule cells which were bound to DNA methylation. DNA methylation and Shh and Notch signaling pathways function cooperatively during cerebellar development. The Notch pathway mainly contributes to the differentiation of Purkinje cells, but Shh is often involved in the development of Bergmann cells. DNA methylation is necessary for the differentiation and migration of granule cells. The expression of Notch1 and Shh in Purkinje cells and Bergmann cells, following the initiation of DNA methylation in granule cells, indicates that DNA methylation is regulated by Notch and Shh pathways during cerebellar development.