Epigenetic regulation of neural crest cell fate
Updated: Jun 19, 2021
To be or not to be a neural crest cell, that is the question.
During early vertebrate embryogenesis, the fertilized egg gradually segregates into distinct cellular lineages. One of these lineages, the neural crest, originates at the juxtaposition of two tissues: the neural plate, which will form the central nervous system, and the non-neural ectoderm, which will form the skin. While it was originally believed that this junction, known as the neural plate border, is comprised of separate zones containing cells already committed to distinct prospective lineages, an alternative possibility was that the cells exist in a naïve state, capable of giving rise to all possible derivatives.
To elucidate how neural crest cells are formed, I characterized the complete gene expression profiles of individual cells derived from the neural plate border (Gandhi et al., eLife, 2020). One previously overlooked gene that was highly expressed in these cells was HMGA1, a chromatin remodeler protein that binds to DNA and modulates the expression of target genes. By deleting Hmga1 at specific timepoints of development, I demonstrated a novel two-pronged mechanism whereby it first governs the switch that commits naïve cells to the neural crest lineage, and later facilitates the separation of neural crest cells from the developing spinal cord, enabling them to migrate to their final destinations in diverse tissues.
Image: (Top) Single-cell RNA-sequencing of the chicken hindbrain can identify distinct lineages that originate from the neural plate border during gastrulation. Hmga1, a chromatin remodeler, is strong expressed in these lineages and its temporally-controlled knockout causes migration defects. (Bottom) The bimodal mechanism by which Hmga1 regulates neural crest formation (left) and migration (right).