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.

中文翻译：

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染色质重塑剂 Hmga1 在神经嵴诱导和 Wnt 依赖性迁移中的双峰功能

在原肠胚形成过程中，神经嵴细胞在神经板边界被指定，以 Pax7 表达为特征。使用单细胞 RNA 测序结合高分辨率原位杂交来识别新的转录调节因子，我们表明染色质重塑 Hmga1 在规范之前高度表达并在迁移的鸡神经嵴细胞中保持。时间控制的 CRISPR-Cas9 介导的敲除揭示了 Hmga1 在神经嵴发育中的两种不同功能。在神经板边界，Hmga1 调节依赖于 Pax7 的神经嵴谱系规范。在迁徙前阶段，第二个作用体现在 Hmga1 损失减少独立于 Pax7 的背神经管的颅嵴迁出。有趣的是，这是由稳定的 ß-catenin 挽救的，因此暗示 Hmga1 是典型的 Wnt 激活剂。