ZFIN ID: ZDB-PUB-040709-8
Combinatorial gene regulation by Bmp and Wnt in zebrafish posterior mesoderm formation
Szeto, D.P., and Kimelman, D.
Date: 2004
Source: Development (Cambridge, England)   131(15): 3751-3760 (Journal)
Registered Authors: Kimelman, David, Szeto, Daniel P.
Keywords: Bmp, Wnt, Posterior mesoderm, T-box genes, Zebrafish
MeSH Terms:
  • Animals
  • Body Patterning*
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • DNA Mutational Analysis
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • In Situ Hybridization
  • Mesoderm/physiology*
  • Oligonucleotides, Antisense/genetics
  • Oligonucleotides, Antisense/metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism*
  • Signal Transduction/physiology*
  • T-Box Domain Proteins
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Wnt Proteins
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 15240553 Full text @ Development
Combinatorial signaling is an important mechanism that allows the embryo to utilize overlapping signaling pathways to specify different territories. In zebrafish, the Wnt and Bmp pathways interact to regulate the formation of the posterior body. In order to understand how this works mechanistically, we have identified tbx6 as a posterior mesodermal gene activated by both of these signaling pathways. We isolated a genomic fragment from the tbx6 gene that recapitulates the endogenous tbx6 expression, and used this to ask how the Bmp and Wnt signaling pathways combine to regulate gene expression. We find that the tbx6 promoter utilizes distinct domains to integrate the signaling inputs from each pathway, including multiple Tcf/LEF sites and a novel Bmp-response element. Surprisingly, we found that overexpression of either signaling pathway can activate the tbx6 promoter and the endogenous gene, whereas inputs from both pathways are required for the normal pattern of expression. These results demonstrate that both Bmp and Wnt are present at submaximal levels, which allows the pathways to function combinatorially. We present a model in which overlapping Wnt and Bmp signals in the ventrolateral region activate the expression of tbx6 and other posterior mesodermal genes, leading to the formation of posterior structures.