title: Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development.
abstract: Mice homozygous for the recessive mutation vestigial tail (vt), which arose spontaneously on Chromosome 11, exhibit vertebral abnormalities, including loss of caudal vertebrae leading to shortening of the tail. Wnt-3a, a member of the wingless family of secreted glycoproteins, maps to the same chromosome. Embryos homozygous for a null mutation in Wnt-3a (Wnt-3a(neo)) have a complete absence of tail bud development and are truncated rostral to the hindlimbs. Several lines of evidence reveal that vt is a hypomorphic allele of Wnt-3a. We show that Wnt-3a and vt cosegregate in a high-resolution backcross and fail to complement, suggesting that Wnt-3a(neo) and vt are allelic. Embryos heterozygous for both alleles have a phenotype intermediate between that of Wnt-3a(neo) and vt homozygotes, lacking a tail, but developing thoracic and a variable number of lumbar vertebrae. Although no gross alteration in the Wnt-3a gene was detected in vt mice and the Wnt-3a coding region was normal, Wnt-3a expression was markedly reduced in vt/vt embryos consistent with a regulatory mutation in Wnt-3a. Furthermore, the analysis of allelic combinations indicates that Wnt-3a is required throughout the period of tail bud development for caudal somitogenesis. Interestingly, increasing levels of Wnt-3a activity appear to be necessary for the formation of more posterior derivatives of the paraxial mesoderm.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, 48109-0618 USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Greco
authors.forename: S
authors.initials: S
authors.lastname: Takada
authors.forename: M M
authors.initials: MM
authors.lastname: Newhouse
authors.forename: J A
authors.initials: JA
authors.lastname: McMahon
authors.forename: A P
authors.initials: AP
authors.lastname: McMahon
authors.forename: S A
authors.initials: SA
authors.lastname: Camper
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D005260:Female; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009115:Muridae; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013131:Spine / Q000196:embryology; D013623:Tail / Q000196:embryology*; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D011506:Proteins; D012333:RNA, Messenger; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse