Disease relevance of Wnt3

• Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland [1].
• No provirus was detected at the int-2, int-3, or Wnt-3 loci [2].
• Mouse Wnt-3 is a proto-oncogene, which is activated by mouse mammary tumor virus (MMTV) [3].

High impact information on Wnt3

• In contrast, signaling by the growth factors Nodal and Wnt3, which are also essential during mouse gastrulation, appears to be normal in lzme embryos [4].
• This phenotype was similar to Wnt-3(-/-) and LRP5/6 double-knockout embryos [5].
• Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge [6].
• In this study, we demonstrate that Wnt3, which is expressed ubiquitously throughout the limb ectoderm, is essential for normal limb development and plays a critical role in the establishment of the AER [6].
• This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors [7].

Biological context of Wnt3

• Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation [8].
• With the addition of these balancers to the previously reported Trp53-Wnt3 balancer, most of mouse chromosome 11 is now available in balancer stocks [9].
• Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells [10].
• Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999) [11].
• The putative amino acid sequences of both proteins are almost 90% identical, but in situ hybridization to mouse embryo sections showed highly restricted patterns of expression of Wnt-3 and Wnt-3A, largely in separate areas in the developing nervous system [7].

Anatomical context of Wnt3

• We have also defined groups of genes regulated by Wnt3/beta-catenin signalling during primitive streak and mesoderm formation [8].
• Whereas Wnt3 mRNA is mainly expressed in the maxillary and medial nasal ectoderm, Wnt9b mRNA is expressed in maxillary, medial nasal, and lateral nasal ectoderm [12].
• Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation [10].
• Wnt3 expression is evident first in the posterior visceral endoderm of 5.5 dpc embryos and later in the posterior epiblast [13].
• We demonstrate here that Wnt3 also is expressed in specific epithelial cell layers in postnatal incisor teeth [14].

Regulatory relationships of Wnt3

• Dlx-1 is expressed in a non-overlapping area immediately anterior to and abutting the Wnt-3 expressing domain, corresponding to the ventral thalamus [15].
• We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult [16].

Other interactions of Wnt3

• A putative effector molecule for WNT3 signaling, the cytoplasmic protein Dishevelled 2 (DVL2), is normally present at high levels in a subset of cells in the outer root sheath and in precursor cells of the hair shaft cortex and cuticle which lie immediately adjacent to Wnt3-expressing cells [17].
• Reciprocal patterns of expression are found within the dorsal thalamus for the Gbx-2 and Wnt-3 genes [18].
• Progeny from an intersubspecies backcross were analyzed to position this locus, termed Shbg, between Il-3 and Int-4 in the middle of this chromosome [19].
• Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis [1].
• Our results reveal that neither Brachyury nor Wnt3 forms a ring of expression in the proximal epiblast as previously thought [13].

Analytical, diagnostic and therapeutic context of Wnt3

• Using long PCR, the genomic region from Wnt3 throughWnt9b was screened in A/WySn for an inserted retrotransposon [20].
• Molecular cloning and characterization of mouse Wnt14b, clustered with mouse Wnt3 in mouse chromosome 11 [21].

References