Follistatin-like-1, a diffusible mesenchymal factor determines the fate of epithelium

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 10; pp. 4601 - 4606
• Main Authors: Umezu, Tomohiro, Yamanouchi, Hiromi, Iida, Yusuke, Miura, Masataka, Tomooka, Yasuhiro, Donahoe, Patricia K.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.03.2010; National Acad Sciences
• Subjects: Animals; Biological Sciences; Capsules; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Line; Cell lines; Cells; Cellular immunity; Coculture Techniques; Developmental biology; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelium; Experimental procedures; Fallopian Tubes - cytology; Female; Follistatin-Related Proteins - genetics; Follistatin-Related Proteins - metabolism; Follistatin-Related Proteins - physiology; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression; Glycoproteins - genetics; Glycoproteins - metabolism; Immunohistochemistry; In Situ Hybridization; Keratin-18 - metabolism; Kidneys; Mesoderm - cytology; Mesoderm - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NIH 3T3 Cells; Oviducts; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Secretory cells; Time Factors; Tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0909501107

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.