| First Author | Camper SA | Year | 1994 |
| Journal | Am J Hum Genet | Volume | 55 |
| Issue | Suppl | Pages | A238 (Abstr.) |
| Mgi Jnum | J:25690 | Mgi Id | MGI:73401 |
| Citation | Camper SA, et al. (1994) Wnt-3a is critical for caudal embryonic development. Am J Hum Genet 55(Suppl):A238 (Abstr.) |
| abstractText | Full text of Abstract. A46 Slide session 46: Gene Structure and Function II. 238. Wnt-3a is critical for caudal embryonic development. S.A. Camper(1), T.L. Greco(1), M.M. Newhouse(1), S. Takada(2), and A.P. McMahon(2). 1 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-0618 and 2 Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138, USA. Skeletal and neural tube defects represent an important class of birth defects. The majority of mouse mutants with neural tube defects also have malformations of the tail. Vestigial tail (vt) is an autosomal recessive mouse mutation characterized by reduction or absence of the tail, vertebral abnormalities, and reduced fertility. The phenotype has been described as the result of failure of cell migration through the primitive streak, causing abnormalities in the development of the neural tube and a reduction in the ventral ectodermal ridge (Gruneburg 1957). Wnt3a is an excellent candidate gene for vt because Wnt3a is expressed in the primitive streak and in the embryonic mesoderm, and it is thought to be involved in cell-to-cell communication and formation of the dorsal-ventral axis in the CNS. A lack of Wnt3a might be expected to result in over-dorsalization of the neural tube and reduction of the ventral ectodermal ridge characteristic of vt/vt embryos. In a high resolution backcross segregating vt, we observed no recombination between vt and Wnt3a in 363 individuals analyzed. In vt/vt mice, Southern blot analysis revealed no abnormalities in the Wnt3a gene, and the Wnt3a cDNA sequence does not encode any amino acid changes. Whole mount in situ hybridization analysis demonstrated that Wnt3a expression is severely reduced in the developing tailbud of day 9.5 vt/vt embryos, suggestive of a lesion in the regulation on Wnt3a expression. Takada et al. recently described a targeted disruption of Wnt3a that results in embryonic lethality at day 10.5-12.5 (1994). The affected fetuses have phenotypic features of caudal regression syndrome, sacrococcygeal dysgenesis and sirenomelia. An alleleism test, carried out by mating vt/vt males with Wnt3a +/Wnt3a-females, demonstrated that vt and Wnt3a are noncomplementing alleles. All of the compound heterozygotes exhibited severe tail defects, including occasional examples of hind limb paralysis and spina bifida. The vertebral defects are intermediate between those of vt and Wnt3a homozygotes, suggesting that the concentration of Wnt3a correlates with the severity of the defect. |
