Miller C, Sassoon D A
Brookdale Center of Developmental and Molecular Biology, One Gustave Levy Place, Box 1126, New York, NY 10029, USA.
Development. 1998 Aug;125(16):3201-11. doi: 10.1242/dev.125.16.3201.
The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350-353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.
在出生后的发育过程中，小鼠雌性生殖道沿前后轴分化。这一过程的标志是输卵管、子宫、子宫颈和阴道中出现不同的细胞类型，并且如早期异种移植实验所示，依赖于特定的间充质 - 上皮相互作用。信号分子Wnt家族的成员最近在这个系统中被鉴定出来，并且已经证明其在生殖道发育中具有早期功能作用。利用ES介导的同源重组技术构建了Wnt - 7a基因缺失的小鼠（帕尔，B. A.和麦克马洪，A. P.（1995年）《自然》374卷，350 - 353页）。由于Wnt - 7a在雌性生殖道中表达，我们研究了雌性生殖道中缺乏Wnt - 7a对发育的影响。我们观察到输卵管与子宫前部缺乏清晰的界限，并获得了子宫角的一些细胞和分子特征。子宫获得了代表正常子宫和阴道之间中间状态的细胞和分子特征。正常阴道有复层上皮，正常子宫有单层柱状上皮，然而，突变子宫有复层上皮。此外，Wnt - 7a突变子宫不形成腺体。在输卵管和子宫中观察到的变化伴随着出生后hoxa - 10和hoxa - 11表达的缺失，这表明Wnt - 7a不是早期hoxa基因表达所必需的，但却是维持表达所必需的。这些成簇的hox基因已被证明在雌性生殖道的前后模式形成中起作用。除了雌性生殖道整体向后移位外，我们还注意到子宫平滑肌排列紊乱，表明沿径向轴的发育受到影响。在形态变化之前，出生时就可检测到其他Wnt基因的边界和水平变化。这些结果表明，一种机制是上皮细胞发出的Wnt - 7a信号维持了雌性生殖道沿前后轴和径向轴不同细胞群体的分子和形态边界。
