New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures

Biomolecules. 2019 Dec 11;9(12):860. doi: 10.3390/biom9120860.


Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient RA signaling gradients that control patterning, cell fate decisions and differentiation. Several steps in the lineage leading to the induction and differentiation of neuromesodermal progenitors and bone-producing osteogenic cells are controlled by RA. Changes to RA signaling activity have effects on the formation of the bones of the skull, the vertebrae and the development of teeth and regeneration of fin rays in fish. This review focuses on recent advances in these areas, with predominant emphasis on zebrafish, and highlights previously unknown roles for RA signaling in developmental processes.

Keywords: calvaria; dentition; neuromesodermal precursors; notochord; osteoblasts; regeneration; retinoic acid; spinal cord; teeth; vertebrae.

Publication types

  • Review

MeSH terms

  • Animal Fins / cytology
  • Animal Fins / metabolism*
  • Animals
  • Bone and Bones / cytology
  • Bone and Bones / metabolism*
  • Cell Differentiation* / genetics
  • Gene Expression Regulation, Developmental
  • Signal Transduction / genetics
  • Tooth / cytology
  • Tooth / metabolism*
  • Tretinoin / chemistry
  • Tretinoin / metabolism*
  • Zebrafish


  • Tretinoin