cis-Regulatory inputs of the wnt8 gene in the sea urchin endomesoderm network

Takuya Minokawa, Athula H. Wikramanayake, Eric H. Davidson

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Expression of the wnt8 gene is the key transcriptional motivator of an intercellular signaling loop which drives endomesoderm specification forward early in sea urchin embryogenesis. This gene was predicted by network perturbation analysis to be activated by inputs from the blimp1/krox gene, itself expressed zygotically in the endomesoderm during cleavage; and by a Tcf1/β-catenin input. The implication is that zygotic expression of wnt8 is stimulated in neighboring cells by its own gene product, since reception of the Wnt8 ligand causes β-catenin nuclearization. Here, the modular cis-regulatory system of the wnt8 gene of Strongylocentrotus purpuratus was characterized functionally, and shown to respond to blockade of both Blimp1/Krox and Tcf1/β-catenin inputs just as does the endogenous gene. The genomic target sites for these factors were demonstrated by mutation in one of the cis-regulatory modules. The Tcf1/β-catenin and Blimp1/Krox inputs are both necessary for normal endomesodermal expression mediated by this cis-regulatory module; thus, the genomic regulatory code underlying the predicted signaling loop thus resides in the wnt8 cis-regulatory sequence. In a second regulatory region, which initiates expression in micromere and macromere descendant cells early in cleavage, Tcf1 sites act to repress ectopic transcription in prospective ectoderm cells.

Original languageEnglish (US)
Pages (from-to)545-558
Number of pages14
JournalDevelopmental Biology
Volume288
Issue number2
DOIs
StatePublished - Dec 15 2005
Externally publishedYes

Keywords

  • cis-regulation
  • Gene network
  • Sea urchin embryo
  • wnt8

ASJC Scopus subject areas

  • Developmental Biology

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