Matrix metalloproteinases regulate mesonephric cell migration in developing XY gonads which correlates with the inhibition of tissue inhibitor of metalloproteinase-3 by Sry.
In the mouse, the sex determining gene Sry, on the Y chromosome, controls testis differentiation during embryogenesis. Following Sry expression, indifferent XY gonads increase their size relative to XX gonads and form cord-like structures with the adjacent mesonephros, providing XY gonad somatic cells. This mesonephric cell migration is known to depend on Sry, but the molecular mechanism of mesonephric cell migration remains unknown. In this study, it was shown that cells expressing Sry induced proliferation of mesonephric cells migrating into male gonads, and inhibited expression of the tissue inhibitor of metalloproteinases (TIMP)-3 gene, which is the endogenous inhibitor of matrix metalloproteinases (MMP). In addition, the mesonephric cell migration was blocked by a chemically synthesized inhibitor of MMP in a gonad/mesonephros organ co-culture system with enhanced green fluorescent protein transgenic embryos. The findings indicate that MMP may play a critical role in mesonephric cell migration, and the function of MMP may be regulated by a Sry-TIMP-3 cascade. These findings are an important clue for the elucidation of testicular formation in developing gonads.
Nishino
Koichiro
K
Laboratory of Applied Genetics, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Yamanouchi
Keitaro
K
Naito
Kunihiko
K
Tojo
Hideaki
H
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D008297:Male; D020782:Matrix Metalloproteinases / Q000502:physiology*; D008650:Mesonephros / Q000166:cytology / Q000196:embryology; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; D013737:Testis / Q000166:cytology / Q000196:embryology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D019717:Tissue Inhibitor of Metalloproteinase-3; D014157:Transcription Factors; D020782:Matrix Metalloproteinases