Bimodal function of chromatin remodeler <i>Hmga1</i> in neural crest induction and Wnt-dependent emigration.

Abstract

During gastrulation, neural crest cells are specified at the neural plate border, as characterized by <i>Pax7</i> expression. Using single-cell RNA sequencing coupled with high-resolution <i>in situ</i> hybridization to identify novel transcriptional regulators, we show that chromatin remodeler <i>Hmga1</i> is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of <i>Hmga1</i> in neural crest development. At the neural plate border, <i>Hmga1</i> regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where <i>Hmga1</i> loss reduces cranial crest emigration from the dorsal neural tube independent of <i>Pax7.</i> Interestingly, this is rescued by stabilized ß-catenin, thus implicating <i>Hmga1</i> as a canonical Wnt activator. Together, our results show that <i>Hmga1</i> functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.