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During gastrulation, neural crest cells are specified at the neural plate border, as characterized by  Pax7  expression. Using single-cell RNA sequencing coupled with high-resolution  in situ  hybridization to identify novel transcriptional regulators, we show that chromatin remodeler  Hmga1  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  Hmga1  in neural crest development. At the neural plate border,  Hmga1  regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where  Hmga1  loss reduces cranial crest emigration from the dorsal neural tube independent of  Pax7.  Interestingly, this is rescued by stabilized ß-catenin, thus implicating  Hmga1  as a canonical Wnt activator. Together, our results show that  Hmga1  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.

Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration