Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development
Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development
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DOI：
10.1101/gad.10.3.313
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发表时间：
1996-02-01
影响因子：
10.5
通讯作者：
Camper, SA
中科院分区：
文献类型：
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作者：
Greco, TL;Takada, S;Camper, SA
在11号染色体上自发产生的隐性突变退化尾（vt）纯合子小鼠表现出椎体异常，包括尾椎丧失导致尾部缩短。Wnt-3a是无翅分泌糖蛋白家族的成员，位于同一条染色体上。Wnt-3a零突变的纯合子胚胎（Wnt-3a(neo)）完全没有尾芽发育，并且吻侧到后肢被截断。多项证据表明，vt是Wnt-3a的一个半形等位基因。我们发现Wnt-3a和vt在高分辨率回交中共分离，但不能互补，这表明Wnt-3a（neo）和vt是等位基因。两个等位基因杂合的胚胎表型介于Wnt-3a（neo）和vt纯合子之间，没有尾巴，但发育胸椎和数量不定的腰椎。尽管在vt小鼠中未检测到Wnt-3a基因的明显改变，且Wnt-3a编码区正常，但在vt/vt胚胎中，Wnt-3a的表达明显降低，这与Wnt-3a的调节性突变一致。此外，等位基因组合分析表明，Wnt-3a在尾芽发育的整个过程中都是尾体细胞发生所必需的。有趣的是，Wnt-3a活性水平的增加似乎是形成更多近轴中胚层后侧衍生物所必需的。
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.