Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads.
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.
Division for Sex Differentiation, Center for Transgenic Animals and Plants, National institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
Masatomo
M
Kusaka
Yuko
Y
Katoh-Fukui
Hidesato
H
Ogawa
Kanako
K
Miyabayashi
Takashi
T
Baba
Yuichi
Y
Shima
Noriyuki
N
Sugiyama
Yukihiko
Y
Sugimoto
Yasushi
Y
Okuno
Ryuji
R
Kodama
Akiko
A
Iizuka-Kogo
Takao
T
Senda
Toshikuni
T
Sasaoka
Kunio
K
Kitamura
Shinichi
S
Aizawa
Ken-ichirou
K
Morohashi
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006066:Gonads / Q000196:embryology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D040081:Protein Array Analysis; D019108:Tight Junctions / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099260:Empty Spiracles Homeobox Proteins
D066246:ErbB Receptors; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins