Molecular mechanism of Pax6-dependent gene control in forebrain and lens development

Abstract

Pax6 is a paired domain (PD) and homeodomain (HD) containing specific DNA binding transcription factor. The amino acid sequences of Pax6 PD and HD are highly conserved throughout evolution. Vertebrate Pax6 and its invertebrate homologous genes (e.g. eyeless and twin of eyeless) have highly conserved functions across different species as "master" regulators of eye development. In addition to the eye, Pax6 regulates development of the central nervous system, olfactory placode, pancreas and pituitary. In the embryonic forebrain, Pax6 plays essential roles in radial glia cell proliferation, pallium-subpallium boundary formation and axon guidance in mice. Disruption of Pax6 results in defects in neural progenitor cell proliferation and forebrain patterning in mice. In the eye, Pax6 regulates differentiation of cornea, iris, lacrimal gland, lens, retina and trabecular meshwork. Ocular lens development serves as a major model to study molecular mechanisms governed by Pax6. Deletion of Pax6 leads to the failure of lens formation in mice. It has been shown that Pax6 regulates key developmental regulators and signaling pathways both in forebrain and lens. However, the gene regulatory networks (GRNs) regulated by Pax6 remain unknown. In addition, the molecular mechanisms of Pax6 in transcriptional activation and repression at the chromatin level have not been fully explored.