PUBLICATION

Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state

Authors
Kherdjemil, Y., Lalonde, R.L., Sheth, R., Dumouchel, A., de Martino, G., Pineault, K.M., Wellik, D.M., Stadler, H.S., Akimenko, M.A., Kmita, M.
ID
ZDB-PUB-161007-8
Date
2016
Source
Nature   539(7627): 89-92 (Journal)
Registered Authors
Akimenko, Marie-Andree
Keywords
Evolutionary developmental biology, Embryology
MeSH Terms
  • Animal Fins/anatomy & histology
  • Animal Fins/metabolism
  • Animals
  • Biological Evolution*
  • Enhancer Elements, Genetic/genetics
  • Extinction, Biological
  • Extremities/anatomy & histology*
  • Female
  • Homeodomain Proteins/metabolism*
  • Introns/genetics
  • Mice
  • RNA, Antisense/biosynthesis
  • RNA, Antisense/genetics
  • Transcription Factors/metabolism
  • Transcription, Genetic
  • Vertebrates/anatomy & histology*
  • Vertebrates/genetics*
  • Zebrafish/anatomy & histology
  • Zebrafish/genetics
PubMed
27706137 Full text @ Nature
Abstract
The fin-to-limb transition represents one of the major vertebrate morphological innovations associated with the transition from aquatic to terrestrial life and is an attractive model for gaining insights into the mechanisms of morphological diversity between species. One of the characteristic features of limbs is the presence of digits at their extremities. Although most tetrapods have limbs with five digits (pentadactyl limbs), palaeontological data indicate that digits emerged in lobed fins of early tetrapods, which were polydactylous. How the transition to pentadactyl limbs occurred remains unclear. Here we show that the mutually exclusive expression of the mouse genes Hoxa11 and Hoxa13, which were previously proposed to be involved in the origin of the tetrapod limb, is required for the pentadactyl state. We further demonstrate that the exclusion of Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the Hoxa11 locus after activation by HOXA13 and HOXD13. Finally, we show that the enhancer that drives antisense transcription of the mouse Hoxa11 gene is absent in zebrafish, which, together with the largely overlapping expression of hoxa11 and hoxa13 genes reported in fish, suggests that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that we observed after expression of Hoxa11 in distal limbs, we propose that the evolution of Hoxa11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping