ZFIN ID: ZDB-PUB-180513-6
A regulatory pathway involving retinoic acid and calcineurin demarcates and maintains joint cells and osteoblasts in the fin regenerate
McMillan, S.C., Zhang, J., Phan, H.E., Jeradi, S., Probst, L., Hammerschmidt, M., Akimenko, M.A.
Date: 2018
Source: Development (Cambridge, England)   145(11): (Journal)
Registered Authors: Akimenko, Marie-Andree, Hammerschmidt, Matthias, Jeradi, Shirine, Zhang, Jing
Keywords: Joints, Osteoblasts, Zebrafish fin regeneration, evx1, hoxa13a, pthlha
MeSH Terms:
  • Animal Fins/growth & development*
  • Animals
  • Calcineurin/metabolism*
  • Cell Differentiation/physiology
  • Homeodomain Proteins/biosynthesis
  • Homeodomain Proteins/genetics
  • Joints/growth & development*
  • Osteoblasts/cytology
  • Parathyroid Hormone-Related Protein/biosynthesis
  • Parathyroid Hormone-Related Protein/genetics
  • Regeneration/physiology*
  • Sp7 Transcription Factor/biosynthesis
  • Sp7 Transcription Factor/genetics
  • Transcription Factors/metabolism
  • Tretinoin/pharmacology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 29752384 Full text @ Development
During zebrafish fin regeneration, blastema cells lining the epidermis differentiate into osteoblasts and joint cells to reconstruct the segmented bony rays. We show that osteoblasts and joint cells originate from a common cell lineage, but are committed to different cell fates. Pre-osteoblasts expressing runx2a/b commit to the osteoblast lineage upon expressing sp7, whereas the strong upregulation of hoxa13a correlates with a commitment to a joint cell type. In the distal regenerate, hoxa13a, evx1 and pthlha are sequentially upregulated at regular intervals to define the newly identified presumptive joint cells. Presumptive joint cells mature into joint-forming cells, a distinct cell cluster that maintains the expression of these factors. Analysis of evx1 null mutants reveals that evx1 is acting upstream of pthlha and downstream of or in parallel with hoxa13a Calcineurin activity, potentially through the inhibition of retinoic acid signaling, regulates evx1, pthlha and hoxa13a expression during joint formation. Furthermore, retinoic acid treatment induces osteoblast differentiation in mature joint cells, leading to ectopic bone deposition in joint regions. Overall, our data reveal a novel regulatory pathway essential for joint formation in the regenerating fin.