PUBLICATION

Thyroid hormone regulates proximodistal patterning in fin rays

Authors
Harper, M., Hu, Y., Donahue, J., Acosta, B., Dievenich Braes, F., Nguyen, S., Zeng, J., Barbaro, J., Lee, H., Bui, H., McMenamin, S.K.
ID
ZDB-PUB-230516-41
Date
2023
Source
Proceedings of the National Academy of Sciences of the United States of America   120: e2219770120e2219770120 (Journal)
Registered Authors
McMenamin, Sarah
Keywords
fin rays, proximodistal patterning, regeneration, thyroid hormone, zebrafish fins
MeSH Terms
  • Animal Fins/physiology
  • Animals
  • Regeneration/physiology
  • Thyroid Hormones/genetics
  • Zebrafish*/physiology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
37186843 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Processes that regulate size and patterning along an axis must be highly integrated to generate robust shapes; relative changes in these processes underlie both congenital disease and evolutionary change. Fin length mutants in zebrafish have provided considerable insight into the pathways regulating fin size, yet signals underlying patterning have remained less clear. The bony rays of the fins possess distinct patterning along the proximodistal axis, reflected in the location of ray bifurcations and the lengths of ray segments, which show progressive shortening along the axis. Here, we show that thyroid hormone (TH) regulates aspects of proximodistal patterning of the caudal fin rays, regardless of fin size. TH promotes distal gene expression patterns, coordinating ray bifurcations and segment shortening with skeletal outgrowth along the proximodistal axis. This distalizing role for TH is conserved between development and regeneration, in all fins (paired and medial), and between Danio species as well as distantly related medaka. During regenerative outgrowth, TH acutely induces Shh-mediated skeletal bifurcation. Zebrafish have multiple nuclear TH receptors, and we found that unliganded Thrab-but not Thraa or Thrb-inhibits the formation of distal features. Broadly, these results demonstrate that proximodistal morphology is regulated independently from size-instructive signals. Modulating proximodistal patterning relative to size-either through changes to TH metabolism or other hormone-independent pathways-can shift skeletal patterning in ways that recapitulate aspects of fin ray diversity found in nature.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping