Department of Biological Science and Technology, and Tissue Engineering Research Center, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4601-6. doi: 10.1073/pnas.0909501107. Epub 2010 Feb 22.
Mesenchyme is generally believed to play critical roles in "secondary induction" during organogenesis. Because of the complexity of tissue interactions in secondary inductions, however, little is known about the precise mechanisms at the cellular and molecular levels. We have demonstrated that, in mouse oviductal development, the mesenchyme determines the fate of undetermined epithelial cells to become secretory or cilial cells. We have established a model for studying secondary induction by establishing clonal epithelial and mesenchymal cell lines from perinatal p53(-/-) mouse oviducts. The signal sequence trap method collected candidate molecules secreted from mesenchymal cell lines. Naive epithelial cells exposed to Follistatin-like-1 (Fstl1), one of the candidates, became irreversibly committed to expressing a cilial epithelial marker and differentiated into ciliated cells. We concluded that Fstl1 is one of the mesenchymal factors determining oviductal epithelial cell fate. This is a unique demonstration that the determination of epithelial cell fate is induced by a single diffusible factor.
间充质通常被认为在器官发生过程中的“次级诱导”中起关键作用。然而，由于次级诱导中组织相互作用的复杂性，对于细胞和分子水平的确切机制知之甚少。我们已经证明，在小鼠输卵管发育中，间充质决定了未确定的上皮细胞成为分泌细胞或纤毛细胞的命运。我们通过从围产期 p53(-/-) 小鼠输卵管建立克隆上皮和间充质细胞系，建立了研究次级诱导的模型。信号序列捕获方法收集了来自间充质细胞系分泌的候选分子。暴露于候选分子之一 Follistatin-like-1 (Fstl1) 的幼稚上皮细胞不可逆地被诱导表达纤毛上皮标志物，并分化为纤毛细胞。我们得出结论，Fstl1 是决定输卵管上皮细胞命运的间充质因子之一。这是一个独特的证明，即上皮细胞命运的决定是由单个可扩散因子诱导的。
