ERNI, BERT, Geminin and their role during neural induction in the chick embryo.

摘要

More than 80 years after the phenomenon of neural induction was first described in the amphibian embryo, the molecular mechanisms responsible for neural differentiation in vertebrates, are still not fully understood. Although the extracellular signals involved in neural induction have been extensively studied during the last decade, very little is known about the downstream intracellular mechanisms of cell specification and commitment. This study uses molecular and embryological techniques, especially the relatively new technique of localized gene missexpression by electroporation, to analyse the role of three coiled-coil domain proteins Geminin, ERNI and BERT, in the activation of the late neural marker Sox2, in the chick embryo. Sox2 encodes a SRY-related transcription factor expressed at the end of gastrulation, in cells of the neural plate, around the time when these cells become committed to their neural fate. In this study, ERNI, BERT and Geminin are found to regulate Sox2 transcription: Geminin is shown to bind to the chromatin remodelling factor Brahma, displacing the HP1□ transcriptional repressor from its binding site and allowing the SWI/SNF chromatin remodelling complex to act as an activator and drive transcription of Sox2. However ERNI interacts with Geminin and recruits onto the complex HP1□, another transcriptional repressor, thus inhibiting Sox2 transcription in the early neural plate. At the end of gastrulation BERT disrupts the interaction between Geminin and ERNI, displacing HP1□ from the SWI/SNF chromatin remodeling complex and allowing it to activate transcription of the late neural marker. These findings provide information that adds to our knowledge of how the process of neural induction takes place in the vertebrate embryo. They also demonstrate a novel molecular mechanism that mediates transcriptional activation at the level of higher order chromatin structure.