Developmental Biology

Changing Sensitivity at the Promoter

Science's STKE  22 May 2001:
Vol. 2001, Issue 83, pp. tw7
DOI: 10.1126/stke.2001.83.tw7

The extracellular ligand Wnt can activate multiple signaling pathways, the classical one being through the frizzled family of receptors, activating Dishevelled and glycogen synthase kinase 3, leading to the accumulation of β-catenin that enters the nucleus and regulates gene expression along with the transcription factors of Tcf/Lef family (see the Wnt/β-catenin pathway by Moon). However, the cellular responsiveness to Wnt changes during development: an example is the loss of dorsalizing activity of Wnt signaling after the midblastula transition (MBT) in Xenopus. Darken and Wilson explored how these different cellular outcomes can arise by manipulating Wnt signaling at different times during the development of Xenopus embryos. Their results indicate that Wnt signaling both before and after MBT is mediated by the classic Wnt pathway, despite the loss of induction of early genes, such as samois and Xnr3, at later stages of development. Expression of an activated Tcf-glucocorticoid fusion construct (which allowed controlled activation of the transcription factor) showed that the ability of TcF to increase the expression of the early genes is lost after the MBT, suggesting that the responsiveness of the late genes' promoters changes after the MBT. A more direct test of this was performed using the promoter of the samois gene fused to a luciferase reporter gene, which also demonstrated a loss of responsiveness to the Tcf-glucocorticoid fusion protein after MBT. Thus, in this instance, the cellular responsiveness is not altered by changing the signaling pathway, but by changes in the target promoters' ability to respond to the signal.

R. Moon, Wnt/beta-catenin pathway, Science's STKE (Connections Map, as seen May 2001), [Online Journal]

R. S. Darken, P. A. Wilson, Axis induction by Wnt signaling: Target promoter responsiveness regulates competence. Dev. Biol. 234, 42-54 (2001). [Online Journal]