PUBLICATION

Molecular dissection of segment formation in the developing hindbrain

Authors
Labalette, C., Wassef, M.A., Desmarquet-Trin Dinh, C., Bouchoucha, Y.X., Le Men, J., Charnay, P., Gilardi-Hebenstreit, P.
ID
ZDB-PUB-141218-7
Date
2015
Source
Development (Cambridge, England)   142: 185-95 (Journal)
Registered Authors
Bouchoucha, Yassine, Charnay, Patrick, Gilardi-Hebenstreit, Pascale, Labalette, Charlotte, Le Men, Johan
Keywords
Egr2, Fgf, Hox, Krox20, Nlz, Rhombomere, Segmentation, Transcriptional enhancer, Zebrafish
MeSH Terms
  • Animals
  • Body Patterning/genetics*
  • Enhancer Elements, Genetic/genetics
  • Gene Expression Regulation, Developmental
  • Models, Biological
  • Rhombencephalon/embryology*
  • Rhombencephalon/metabolism*
  • Signal Transduction/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
25516974 Full text @ Development
Abstract
Although many components of the genetic pathways that provide positional information during embryogenesis have been identified, it remains unclear how these signals are integrated to specify discrete tissue territories. Here, we investigate the molecular mechanisms underlying the formation of one of the hindbrain segments, rhombomere (r) 3, specified by the expression of the gene krox20. Dissecting krox20 transcriptional regulation has identified several input pathways: Hox paralogous 1 (PG1) factors, which both directly activate krox20 and indirectly repress it via Nlz factors, and the molecular components of an Fgf-dependent effector pathway. These different inputs are channelled through a single initiator enhancer element to shape krox20 initial transcriptional response: Hox PG1 and Nlz factors define the anterior-posterior extent of the enhancer's domain of activity, whereas Fgf signalling modulates the magnitude of activity in a spatially uniform manner. Final positioning of r3 boundaries requires interpretation of this initial pattern by a krox20 positive-feedback loop, orchestrated by another enhancer. Overall, this study shows how positional information provided by different patterning mechanisms is integrated through a gene regulatory network involving two cis-acting elements operating on the same gene, thus offering a comprehensive view of the delimitation of a territory.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping