QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online June 22, 2006
doi: 10.1242/10.1242/dev.02452

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by He, X. Articles by Axelrod, J. D. Search for Related Content PubMed PubMed Citation Articles by He, X. Articles by Axelrod, J. D.

A WNTer wonderland in Snowbird

¹ Neurobiology Program, Children's Hospital and Harvard Medical School, Boston, MA 02115-5724, USA.
² Pathology Department, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.

View larger version (25K): [in a new window]   Fig. 1. Wnt biogenesis and interaction with receptors. (A) Wnt biogenesis for short- and long-range signaling. Wnt palmitoylation occurs within the endoplasmic reticulum (ER) and requires Porcupine (Porc). Wntless (Wls) probably acts in the Golgi apparatus and exocytic vesicles (EV), and is required for Wnt to reach the cell surface for secretion (Banziger et al., 2006; Bartscherer et al., 2006). VPS-35 and the retromer complex appears to be required only for Wnt (EGL-20) destined for long-range signaling (Coudreuse et al., 2006; Prasad and Clark, 2006). (B) In the absence of Wnt, ß-catenin is unstable. (C) The association of Wnt with the Fz-Lrp5/6 co-receptor complex stabilizes ß-catenin, via the sequential phosphorylation (P) of the Lrp5/6 cytoplasmic domain, likely by Gsk3 and Ck1 (Davidson et al., 2005; Zeng et al., 2005), to activate the canonical pathway. Lrp5/6 phosphorylation recruits the scaffolding protein Axin (Mao et al., 2001; Tamai et al., 2004). Dishevelled (Dvl) may act via the recruitment or inhibition of the Axin complex. Wnt5a can bind Ror2, and antagonize Tcf/ß-catenin transcription downstream of ß-catenin stabilization (Mikels and Nusse, 2006).

View larger version (23K): [in a new window]   Fig. 2. Nuclear Tcf/ß-catenin complexes. (A) In the absence of Wnt stimulation, Tcf binds to the WRE (Wnt responsive element) but recruits Groucho-HDAC to repress Wnt responsive genes. CtBP is involved in this repression but acts in parallel to Tcf (Fang et al., 2006). (B) On Wnt stimulation, stabilized ß-catenin complexes with Tcf and recruits multiple co-activator complexes for transcriptional activation (Mosimann et al., 2006; Sierra et al., 2006). (C) When wild-type APC is expressed in cancer cells that harbor a mutant APC, wild-type APC directly inhibits Myc expression (Sierra et al., 2006) by recruiting CtBP to the Myc promoter (Sierra et al., 2006). A transcriptional repressor, YY1, and the E3 ubiquitin ligase subunit ß-Trcp, which is required for ß-catenin degradation, are also recruited to the Myc promoter (Sierra et al., 2006). The mechanism by which many of these events occur remains unknown. APC may also act together with CtBP to remove ß-catenin from Tcf (Hamada and Bienz, 2004).

View larger version (70K): [in a new window]   Fig. 3. Wnt in regeneration. (A,B) Inverse gradients of Wnt and Dkk proteins in Hydra pattern formation during budding and regeneration. (C,D) Overlapping ring-like expression domains of hyWntA (C) and hywnt6 (D) during Hydra bud formation (H. Bode and T. Holstein, unpublished). (E,F) Zebrafish tail fin regeneration, which requires Wnt/ß-catenin signaling (R. Moon, personal communication). Image courtesy of Christi Stoick, University of Washington, Seattle, WA, USA. (A) Reproduced, with permission, from Hobmayer et al. (Hobmayer et al., 2000). (B) Reproduced, with permission, from Guder et al. (Guder et al., 2006).