Function of chromatin modifier Hmgn1 during neural crest and craniofacial development

Genesis. 2021 Oct;59(10):e23447. doi: 10.1002/dvg.23447. Epub 2021 Sep 3.

Abstract

The neural crest is a dynamic embryonic structure that plays a major role in the formation of the vertebrate craniofacial skeleton. Neural crest formation is regulated by a complex sequence of events directed by a network of transcription factors working in concert with chromatin modifiers. The high mobility group nucleosome binding protein 1 (Hmgn1) is a nonhistone chromatin architectural protein, associated with transcriptionally active chromatin. Here we report the expression and function of Hmgn1 during Xenopus neural crest and craniofacial development. Hmgn1 is broadly expressed at the gastrula and neurula stages, and is enriched in the head region at the tailbud stage, especially in the eyes and the pharyngeal arches. Hmgn1 knockdown affected the expression of several neural crest specifiers, including sox8, sox10, foxd3, and twist1, while other genes (sox9 and snai2) were only marginally affected. The specificity of this phenotype was confirmed by rescue, where injection of Hmgn1 mRNA was able to restore sox10 expression in morphant embryos. The reduction in neural crest gene expression at the neurula stage in Hmgn1 morphant embryos correlated with a decreased number of sox10- and twist1-positive cells in the pharyngeal arches at the tailbud stage, and hypoplastic craniofacial cartilages at the tadpole stage. These results point to a novel role for Hmgn1 in the control of gene expression essential for neural crest and craniofacial development. Future work will investigate the precise mode of action of Hmgn1 in this context.

Keywords: Xenopus; craniofacial; neural crest; sox10; transcription; twist1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatin / genetics
  • Embryo, Nonmammalian
  • Embryonic Development / genetics*
  • Forkhead Transcription Factors / genetics
  • Gastrula / growth & development
  • Gastrula / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Gene Knockdown Techniques
  • HMGN1 Protein / antagonists & inhibitors
  • HMGN1 Protein / genetics*
  • Neural Crest / growth & development*
  • Neural Crest / metabolism
  • SOX9 Transcription Factor / genetics
  • SOXE Transcription Factors / genetics*
  • Transcription Factors / genetics
  • Twist-Related Protein 1 / genetics*
  • Xenopus Proteins / genetics*
  • Xenopus laevis / genetics
  • Xenopus laevis / growth & development

Substances

  • Chromatin
  • Forkhead Transcription Factors
  • HMGN1 Protein
  • SNAI2 protein, Xenopus
  • SOX9 Transcription Factor
  • SOXE Transcription Factors
  • Sox8 protein, Xenopus
  • Transcription Factors
  • Twist-Related Protein 1
  • Xenopus Proteins
  • foxd3b-A protein, Xenopus
  • twist basic helix-loop-helix transcription factor 1, Xenopus