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Wnt signaling pathway diagram

Wnt. See the simplified map for a further selection. It becomes hard to include all of these new components and the list below is selective. Wls/Evi . Porc.updated June 2010 The Wnt pathway is increasingly becoming more complex and new participants are still being uncovered.

beta-catenin . Porcupine has some homology to a family of o-acyl transferases and may be involved in lipid modification of Wnt proteins (Hofmann. 1997) resemble the ligand binding domains of the Frizzled receptor. their proteins will be made in any cell type.2001. elegans. Zeng et al (2008) propose a role for Dsh and Fz in this process as well. 2001. 1996). 2000. and can bind to WntFrizzled to form a ternary complex (Wehrli et al. 2003. reviewed by Nusse. Frizzled. 2005 . Frp. 2006. A special form of monounsaturated palmitoylation has been detected on a serine residue in the Wnt protein (Takada 2006) The Porcupine (Porc) protein may be involved in secretion or ER transport. in a Wnt and phosphorylation dependent manner (Mao et al. Dickkopf (Dkk) in Xenopus antagonizes Wnt action (Glinka1998Fedi. beta-catenin levels are kept low through interactions with the protein kinase GSK- . There is control over the secretion and processing of the Wnt protein.LRP (or arrow) is required for Wnt signaling as well. Tolwinsky. 2004). given the role of the pre-renon receptor as an adaptor between Wnt receptors and the vacuolar H+adenosine triphosphatase (V-ATPase) complex (Cruciat. APC. GSK3. WTX. In cells not exposed to the signal. In addition to porcupine. 1992). 2010). van den Heuvel 1993). 2000. 2005.Even though there is control over Wnt secretion. Wnt signaling at the level of receptor interactions and activity may be associated with intracellular compartments such as vacuoles. their expression is not restricted to dedicated cells. 1999) by binding to LRP (Mao et al. Willert 2003. WIF. In Drosophila as well as in vertebrates. Pinson et al. the porcupine homolog mom-1has a similar function in promoting secretion of the Wnt protein Mom-2 (Rocheleau 1997).The specificity between Wnts and receptor complexes is determined by the Frizzled class of receptors (Bhanot. The cytoplasmic tail of LRP can bind to Axin. 2001. Axin. there is no evidence that the function of genes like porcupine and Wls/Evi is restricted to particular cells implying that once Wnt genes are expressed. Tamai et al. The Wnt signal leads. Wnt proteins are modified by palmitoylation (Willert 2003) and glycosylation (Mason. 2001). several secreted proteins can bind directly to Wnts. Dkk In the extracellular space. Semenov et al.. beta-TrCP Armadillo/beta-catenin is the key mediator of the Wnt signal. as Wingless is retained in the ER in porcupinemutant Drosophila embryos (Kadowaki 1996. 2000). 2004. 2006). WIFs form another group of secreted Wnt binding factors (Hsieh 1999). In C. 2000: Tamai et al. 2001). Davidson 2005. Dsh Wnts interact genetically and biochemically with a complex of receptors. several other proteins.Wnt genes can be expressed in many different cell types. Bafico et al. of which the CRD (cysteine-rich domain) is the primary ligand binding domain (Dann et al. to modulate Wnt activity. LRP/Arrow. Zhai. Phosphorylation of the tail of LRP is regulated by two protein kinases: GSK3 and CK1gamma (Zeng. including the transmembrane Wls/Evi are specifically involved in Wnt secretion (Banziger. through its receptor to activation of Dishevelled (Dsh). Takada 2006). Bartscherer. The secreted Frps (Rattner.

The stabilizedbeta-catenin then enters the nucleus (Tolwinski and Wieschaus. 1998 Itoh 1998. also in C. Axin and Zw3/GSK.TCFacts as a repressor of Wnt/Wg target genes (Brannon 1997. Brg-1 is a mammalian SWI/SNF and Rsc chromatin-remodelling complex protein binding tobeta-catenin and promoting activity (Barker. 1999). elegans Lin 1998)..Parker 2002). APC and Axin (Behrens. Daniels and Weis (2005) have shown that beta-catenin displaces Groucho from TCF. 2004) to interact with TCF. 2000.     Main Forum Contact Nusse Lab All rights reserved © Site design by Roel Nusse and Xinhong Lim Skip to Main Content Area . Marikawa 1998. and promotes interactions between Dsh and Axin (Hsu 1999. Liu 2002.. CK1a. The DIX domain in Axin is similar to the NH2 terminus in Dsh.3b. Amit 2002). Groucho. which may be the regulatory step in the inactivation of Zw3/GSK (Salic.) Another player in this complex is the Wilms tumor suppressor gene WTX (Major.). Goentero and Kirschner (2009) have shown that abolute levels of beta-catenin are less important than fold-changes in determining activity of Wnt signaling in target cells (reviewed by Ferrell. Pygo. 2004) may also play a role in rearranging this complex. Wnt signaling initially leads to a complex between Dsh. releasing it from the Axin complex and accumulation (Salic.. 2001. Thompson 2002. Lgs. Farr 2000). listed in a separate table. Rivera. 2009). Brg-1. As a consequence.Riese 1997. through the ubiquitin pathway (Aberle 1997. 2000). 1999.Hamada. Hyx In the nucleus. Binding of Axin to the cytoplasmic tail of LRP in a Wnt dependent manner (Mao et al. in the absence of the Wnt signal. Tamai et al. involving interactions with beta-TrCP(Jiang 1998. 2000). TCF. Tolwinski 2003.beta-catenin can convert TCF into a transcriptional activator of the same genes that are repressed by TCF alone (reviewed in Nusse. Two other key players in this complex are Legless (Bcl9)and Pygopos (Kramps 2002. 2007. 1999).Smalley. leading to cell transformation (reviewed in Polakis. GSK does not phosphorylatebeta-catenin anymore.Bienz 1998 . 2001) There are many target genes of the Wnt pathway. GBP/Frat1. after phosphorylation by GSK-3 and CK1 alpha (Yanagawa 2002. 2007) beta-catenin is degraded. Loss of APC in mammalian cells can also lead to a critical loss over beta-catenin control. TCF can form a complex with Groucho (Cavallo 1998). reviewed inManiatis 1999) In a current model.

2010 See History for timeline additions Search this site: Search form-e69be5f33e4 search_block_form     Home Mouse Wnt genes Updated December 2009 There are 19 Wnt genes in the mouse genome.2010 Roel Nusse Last updated: October. Most genes linked to MGI.Login/Register 1997 . Mouse Genome Informatics. . There is a separate table for syntenic linkage groups. See thecomparative table of all vertebrate Wnt genes for an explanation of the numbering/nomenclature.

1996 Defective lung development (with Wnt2b. 2008) . 2009)    Wnt3 early gastrulation defect. see alignments of many Wnt proteins gene natural allele Phenotype of Knockouts or other functions   loss midbrain. 2000) Segmentation oscillation clock (Aulehla 2003) Left right asymmetry (Nakaya 2005) HSC self-renewal defect (Luis. 2005 Defective lung development (with Wnt2b. reduction in dorsolateral neural precursors in the neural tube together with Wnt-1 KO Ikeya M.  decrease in the number of thymocytes (with Wnt-4 deletion. loss cerebellum McMahon 1990 Thomas KR. 1990. Axis formation (Liu P. 2009)  Wnt2b/13 retinal cell differentiation Kubo. reduction in dorsolateral neural precursors in the neural tube together with Wnt-3A KO Ikeya M. 2005)     somites. McMahon 1992 Wnt1 (previously called int-1) swaying Thomas. tailbud defects (Takada. 2003. 2001) vestigial Wnt3a tail Greco 1996  deficiency in neural crest derivatives. Kubo. Goss. 1997 ) through loss expression Brachyury (Yamaguchi et al. Millar 1999 Defect in establishing the AER (Barrow. 2005) hippocampal neurogenesis (Lie. et al.Mulroy 2002) Wnt2 (previously called irp)   placental defects Monkley. 2003) medial-lateral retinotectal topography (Schmitt.     Loss hippocampus (Lee et al. 1991 deficiency in neural crest derivatives. M.Also. 1999) This is mediated by Lef-1 (Galceran. 1999. Goss. personal communication) Hair growth Kishimoto 2000. 1994 Greco 1996 Yoshikawa Y. Capecchi. et al.

Ectopic Testosterone synthesis in females. truncated AP axis. Lyuksyutova et al. absence Mullerian Duct. longitudinal skeletal outgrowth (Yang. failure regression of the Mullerian duct because the receptor for Mullerian-inhibiting substance is not expressed. 2009 Wnt5b Wnt6 postaxial Wnt7a hemimelia Parr 1998   limb polarity (Parr 1995) female infertility. 2009 endothelial differentiation of ES cells Yang.Parr 1998  maintenance appropriate uterine patterning during . Vainio S. 2004) shortened and widened cochlea (planar polarity) Qian 2007 Mammary gland phenotype (Roarty. 2000) decrease in the number of thymocytes (with Wnt-1 deletion.  kidney defects Stark K.           truncated limbs. 2007 Sex determination (Kim 2006) defects in female development. 2003). reduced number proliferating cells Yamaguchi 1999 Distal lung morphogenesis (Li. 2002) Chondrocyte differentiation. 2007) prostate gland development Huang 2009 intestinal elongation Cervantes. Mulroy 2002) Repression of the migration of steroidogenic adrenal precursors into the gonad Jeays-Ward 2003 Anterior-posterior guidance of commissural axons (not tested in Wnt4 mutant. et al 1999 Wnt4     side-branching in mammary gland (Brisken. renal vesicle induction Park. 1994. 2003) Inhibits B cell proliferation and functions as a tumor suppressor (Liang 2003) Wnt5a Defects in posterior growth of the female reproductuve tract (Mericskay et al.

2009) Wnt8a  Wnt8b  Loss of function mutant: no effect on neural development. Stenman 2008) Placental developmental defects (Parr. 2001) Respiratory failure. 2000) High levels cell death in response to DES in the Female Reproductive Tract (Carta L. 2007 planar cell polarity of the kidney epithelium (Karner. Liebner 2008) cortico-medullary axis in the kidney (Yu et al. 2005) also in LRP5 and LEF1 mutants)    Lung development (Rajagopal 2008) CNS vasculature (with Wnt7a. 2002) macrophage-induced programmed cell death (Lobov. 2005)  (prev. Sassoon D. 2009)  Wnt10a . Wnt14) Loss of function mutant: Joint integrity (Spater 2006)  Wnt9b regulation of mesenchymal to epithelial transitions (Carroll. Wnt15) renal vesicle induction Park. (Fotaki. defects in early mesenchymal proliferation leading to lung hypoplasia (Shu.the development of the mouse female reproductive tract (Miller 1998)   Delayed maturation synapses in Cerebellum (Hall. 2004)      Wnt7b May promote neuronal differentiation (Hirabayashi 2004) CNS vasculature (with Wnt7b. 2009) Wnt9a  (prev. Stenman 2008. but changes in gene expression.

2000 Ureteric branching defects (Majumdar.  Wnt10b Taste Papilla Development (Iwatsuki. 2005) Overexpression inhibits adipogenesis Ross. 2003) Kispert A 1996 Wnt11  Cardiogenesis Pandur 2002 Wnt16 Activated by E2A-Pbx1 fusion protein in Pre-B ALL McWhirter 1999     Main Forum Contact Nusse Lab All rights reserved © Site design by Roel Nusse and Xinhong Lim . 2007) Loss of function mutant: decreased trabecular bone (Bennett 2005)    Loss gene promotes Coexpression of Myogenic and Adipogenic program (Vertino.

2003) In the following table. There are additional tables for each species and a separate table for syntenic linkage groups for mouse and human genes.Skip to Main Content Area Login/Register 1997 .2010 Roel Nusse Last updated: October. See alignments Wnts Wnt genes in Vertebrates gene Wnt1 Mouse Human Xenopus Chicken Zebrafish ♦ ♦ ♦ ♦ ♦ . April . 2010 See History for timeline additions Search this site: Search form-03bc5e83ef87 search_block_form     Home Vertebrate Wnt genes Comparative table of all vertebrate Wnt genes (upd. the red diamond ♦ indicates that the particular Wnt gene has been identified. See the footnotes for more info.

Wnt14. see below Wnt-16 notes . Wnt13. Wnt15 have all been renamed.Wnt2 Wnt2B Wnt3 Wnt3A Wnt4 Wnt4B Wnt5A Wnt5B Wnt6 Wnt7A Wnt7B Wnt7C ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ gene Wnt8A Wnt8B Wnt9A Wnt9B Wnt10A Wnt10B Wnt11 Mouse Human Xenopus Chicken Zebrafish ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ Wnt12.

Wnt9 was initially only isolated from Hagfisch (Eptatretus stouti) and Thresher Shark (Alopius vulpinus) Sidow 1992. T. (1992) and it should be called Wnt-10B. Wnt14 and Wnt15 have therefore been renamed into Wnt9A and Wnt9B. The gene called human Wnt-13 (Katoh et al. as these genes are very similar. 1996) is very similar to the human Wnt-2 and is better named Wnt-2B.1. 2. The first Wnt-2 cloned from Xenopus is called XWnt-2 Wolda. and Moon. but is actually the ortholog of the human and mouse Wnt-2. R. A gene called Wnt-12 identified by Adamson et al is the same as reported by Lee et al. 3. S. nor have separate orthologs of CWnt-8C been cloned from the mouse and the human. and Wang and Shackleford. In addition. The chicken Wnt-8C is probably the true ortholog of Xenopus Wnt-8A. and called Wnt-10B. 4. A Xenopus Wnt-2 cloned by Landesman Y and Sokol SY (1997) is called XWnt-2B. L. S. T. Hardiman et al. It was realized byQian et al (2003) that the genes first called Wnt14 and Wnt15 are orthologs of Wnt9. (1992) but it is the ortholog of Wnt-2B/Wnt13. L. As this mouse Wnt gene is indeed very similar to Wnt-10 genes cloned from Xenopus and Zebrafish (Wolda. and Moon. there are no other chicken Wnt-8 genes yet. R.     Main Forum Contact Nusse Lab All rights reserved © Site design by Roel Nusse and Xinhong Lim .

Also. links restored October 2009) Note: there are 19 human Wnt genes altogether There is a separate table for syntenic linkage groups. see alignments of Wnt proteins Linked to HUGO WNT1 WNT2 WNT2B/13 WNT3 WNT3A Mullerian-duct regression and virilization (Biason-Lauber 2004) Tetra-Amelia (Niemann 2004) Disease WNT4 SERKAL syndrome (Mandel. See the comparative table of all vertebrate Wnt genes for and explanation of the numbering/nomenclature. 2008) WNT5A Associated with Susceptibility to type 2 diabetes (Kanazawa 2004) WNT5B WNT6 WNT7A WNT7B Fuhrmann syndrome .Human Wnt genes (updated.

Bohring.WNT8A WNT8B WNT9A (previously WNT14) WNT9B Previously WNT15) Odonto-onychodermal dysplasia Adaimy. 2007 . 2009 Â Mutations in Obesity patients Christodoulides 2006 WNT10A WNT10B Split-Hand/Foot Malformation (Ugur 2008) WNT11 WNT16 .

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