Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development.
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.
Greco
T L
TL
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, 48109-0618 USA.
Takada
S
S
Newhouse
M M
MM
McMahon
J A
JA
McMahon
A P
AP
Camper
S A
SA
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
D011506:Proteins; D012333:RNA, Messenger; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse