Abnormal epithelial cell polarity and ectopic Epidermal Growth Factor Receptor (EGFR) expression induced in Emx2 KO Embryonic Gonads

Masatomo Kusaka, Yuko Katoh-Fukui, Hidesato Ogawa, Kanako Miyabayashi, Takashi Baba, Yuichi Shima, Noriyuki Sugiyama, Yukihiko Sugimoto, Yasushi Okuno, Ryuji Kodama, Akiko Iizuka-Kogo, Takao Senda, Toshikuni Sasaoka, Kunio Kitamura, Shinichi Aizawa, Ken Ichirou Morohashi

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42 Citations (Scopus)

Abstract

The gonadal primordium first emerges as a thickening of the embryonic coelomic epithelium, which has been thought to migrate mediodorsally to form the primitive gonad. However, the early gonadal development remains poorly understood. Mice lacking the paired-like homeobox gene Emx2 display gonadal dysgenesis. Interestingly, the knockout (KO) embryonic gonads develop an unusual surface accompanied by aberrant tight junction assembly. Morphological and in vitro cell fate mapping studies showed an apparent decrease in the number of the gonadal epithelial cells migrated to mesenchymal compartment in the KO, suggesting that polarized cell division and subsequent cell migration are affected. Microarray analyses of the epithelial cells revealed significant up-regulation of Egfr in the KO, indicating that Emx2 suppresses Egfr gene expression. This genetic correlation between the two genes was reproduced with cultured M15 cells derived from mesonephric epithelial cells. Epidermal growth factor receptor signaling was recently shown to regulate tight junction assembly through sarcoma viral oncogene homolog tyrosine phosphorylation. We show through Emx2 KO analyses that sarcoma viral oncogene homolog tyrosine phosphorylation, epidermal growth factor receptor tyrosine phosphorylation, and Egfr expression are up-regulated in the embryonic gonad. Our results strongly suggest that Emx2 is required for regulation of tight junction assembly and allowing migration of the gonadal epithelia to the mesenchyme, which are possibly mediated by suppression of Egfr expression.

Original languageEnglish
Pages (from-to)5893-5904
Number of pages12
JournalEndocrinology
Volume151
Issue number12
DOIs
Publication statusPublished - Dec 2010

All Science Journal Classification (ASJC) codes

  • Endocrinology

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    Kusaka, M., Katoh-Fukui, Y., Ogawa, H., Miyabayashi, K., Baba, T., Shima, Y., Sugiyama, N., Sugimoto, Y., Okuno, Y., Kodama, R., Iizuka-Kogo, A., Senda, T., Sasaoka, T., Kitamura, K., Aizawa, S., & Morohashi, K. I. (2010). Abnormal epithelial cell polarity and ectopic Epidermal Growth Factor Receptor (EGFR) expression induced in Emx2 KO Embryonic Gonads. Endocrinology, 151(12), 5893-5904. https://doi.org/10.1210/en.2010-0915