PUBLICATION

Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors

Authors
Delporte, F.M., Pasque, V., Devos, N., Manfroid, I., Voz, M.L., Motte, P., Biemar, F., Martial, J.A., and Peers, B.
ID
ZDB-PUB-080527-1
Date
2008
Source
BMC Developmental Biology   8: 53 (Journal)
Registered Authors
Biemar, Frédéric, Delporte, Francois, Devos, Nathalie, Manfroid, Isabelle, Martial, Joseph A., Peers, Bernard, Voz, Marianne
Keywords
none
MeSH Terms
  • Repressor Proteins/genetics*
  • Multiprotein Complexes
  • Retina/embryology
  • Retina/metabolism
  • Trans-Activators/chemistry
  • Trans-Activators/metabolism
  • Conserved Sequence
  • Promoter Regions, Genetic
  • Homeodomain Proteins/chemistry
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Molecular Sequence Data
  • Sequence Homology, Nucleic Acid
  • Animals
  • Transcription Factors/chemistry
  • Transcription Factors/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Telencephalon/embryology
  • Telencephalon/metabolism
  • Animals, Genetically Modified
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Base Sequence
  • Eye Proteins/genetics*
  • DNA-Binding Proteins/chemistry
  • DNA-Binding Proteins/metabolism
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Pancreas/embryology
  • Pancreas/metabolism*
  • Paired Box Transcription Factors/genetics*
(all 40)
PubMed
18485195 Full text @ BMC Dev. Biol.
Abstract
BACKGROUND: PAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements. RESULTS: Due to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1. CONCLUSIONS: Our data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair.
Genes / Markers
Figures
Figure Gallery (9 images)
Show all Figures
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ulg302TgTransgenic Insertion
    ulg515TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      1 - 3 of 3
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRedEFGDsRed
      GFPEFGGFP
      1 - 2 of 2
      Show
      Mapping
      No data available