2025-06-23 カリフォルニア工科大学(Caltech)
An injured and uninjured zebrafish heart with cells stained.Credit: M. Martik
<関連情報>
- https://www.caltech.edu/about/news/genetic-code-enables-zebrafish-to-mend-damaged-organs
- https://www.pnas.org/doi/10.1073/pnas.2423697122
ゼブラフィッシュ心臓再生における胚性心臓神経堤転写プロファイルの再活性化 Reactivation of an embryonic cardiac neural crest transcriptional profile during zebrafish heart regeneration
Rekha M. Dhillon-Richardson, Alexandra K. Haugan, Luke W. Lyons, +2 , and Megan L. Martik
Proceedings of the National Academy of Sciences Published:June 18, 2025
DOI:https://doi.org/10.1073/pnas.2423697122
Significance
Many common human congenital heart defects are linked to problems that arise during cardiac neural crest (CdNC) development. Here, we use the zebrafish, which has the remarkable ability to regenerate their adult heart, to understand the genetic programs that control cardiac development and adult repair. We identify a set of genes that control the development of the CdNC and find that these genes are reactivated after heart injury in the adult zebrafish. Unlike the zebrafish, human hearts have a very limited ability to regenerate after injury. Our findings in zebrafish can provide insight into potential clinical interventions for congenital heart defects and adult heart damage.
Abstract
During vertebrate development, the heart primarily arises from mesoderm, with crucial contributions from cardiac neural crest (CdNC) cells that migrate to the heart and form a variety of cardiovascular derivatives. Here, by integrating bulk and single cell RNA-seq with ATAC-seq, we identify a gene regulatory subcircuit specific to migratory cardiac crest cells composed of key transcription factors egr1, sox9a, tfap2a, and ets1. Notably, we show that cells expressing the canonical neural crest gene sox10 are essential for proper cardiac regeneration in adult zebrafish. Furthermore, expression of all transcription factors from the migratory cardiac crest gene subcircuit are reactivated after injury at the wound edge. Together, our results uncover a developmental gene regulatory network that is important for CdNC fate determination, with key factors of the program reexpressed during regeneration.
