PUBLICATION

A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates

Authors
Parker, H.J., De Kumar, B., Green, S.A., Prummel, K.D., Hess, C., Kaufman, C.K., Mosimann, C., Wiedemann, L.M., Bronner, M.E., Krumlauf, R.
ID
ZDB-PUB-190406-3
Date
2019
Source
Nature communications   10: 1189 (Journal)
Registered Authors
Bronner-Fraser, Marianne, Hess, Christopher, Krumlauf, Robb, Mosimann, Christian, Prummel, Karin
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Binding Sites/genetics
  • Cell Line
  • Conserved Sequence/physiology
  • Enhancer Elements, Genetic/genetics
  • Gene Expression Regulation, Developmental/physiology*
  • Genes, Homeobox/physiology*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Lampreys
  • Mice
  • Mouse Embryonic Stem Cells
  • Neural Crest/embryology*
  • Neural Crest/metabolism
  • Sequence Alignment
  • Vertebrates/embryology
  • Vertebrates/genetics*
  • Zebrafish
PubMed
30867425 Full text @ Nat. Commun.
Abstract
In jawed vertebrates (gnathostomes), Hox genes play an important role in patterning head and jaw formation, but mechanisms coupling Hox genes to neural crest (NC) are unknown. Here we use cross-species regulatory comparisons between gnathostomes and lamprey, a jawless extant vertebrate, to investigate conserved ancestral mechanisms regulating Hox2 genes in NC. Gnathostome Hoxa2 and Hoxb2 NC enhancers mediate equivalent NC expression in lamprey and gnathostomes, revealing ancient conservation of Hox upstream regulatory components in NC. In characterizing a lamprey hoxα2 NC/hindbrain enhancer, we identify essential Meis, Pbx, and Hox binding sites that are functionally conserved within Hoxa2/Hoxb2 NC enhancers. This suggests that the lamprey hoxα2 enhancer retains ancestral activity and that Hoxa2/Hoxb2 NC enhancers are ancient paralogues, which diverged in hindbrain and NC activities. This identifies an ancestral mechanism for Hox2 NC regulation involving a Hox-TALE regulatory circuit, potentiated by inputs from Meis and Pbx proteins and Hox auto-/cross-regulatory interactions.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping