Histone Deacetylase activity plays an essential role in establishing and maintaining the vertebrate neural crest

Abstract

The Neural Crest, a progenitor population that drove vertebrate evolution, retains the broad developmental potential of the blastula cells it is derived from, even as neighboring cells undergo lineage-restriction. The mechanisms that enable these cells to preserve their developmental potential remain poorly understood. Here we explore the role that Histone Deacetylase (HDAC) activity plays in this process. We show that HDAC activity is essential for formation of neural crest, as well as for proper patterning of the early ectoderm. The requirement for HDAC activity initiates in naïve blastula cells; HDAC inhibition causes loss of pluripotency gene expression, and blocks the ability of blastula stem cells to contribute to lineages of the three embryonic germ layers. We find that pluripotent naïve blastula cells and neural crest cells are both characterized by low levels of histone acetylation, and show that increasing HDAC1 levels enhances the ability of blastula cells to be reprogrammed to a neural crest state. Together, these findings elucidate a previously uncharacterized role for HDAC activity in establishing the neural crest stem cell state.