Abstract
Fibroblast growth factor 9 (FGF9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the XY gonad, but neither it nor the FGF receptors is expressed sex-specifically. Of the Sprouty genes encoding antagonists of receptor tyrosine kinases including FGFr, mSprouty2 expression was confined to the developing testis and mesonephros. Gain of SPROUTY2 function in the male genital ridge and mesonephros malformed the vas deferens and epididymis, and diminished the number of seminiferous tubules and interstitium associating with reduced mesonephric cell migration and Fgf9 expression in embryonic testis, whereas exogenous FGF9 signaling recovered mesonephric cell migration inhibited by SPROUTY2. These phenotypes associated also with the decreased expression of Sox9, Desert hedgehog, Hsd3beta, Platelet/endothelial cell adhesion molecule, and alpha-smooth muscle actin, which are markers of the Sertoli, Leydig, endothelial, and peritubular myoid cells of the developing testis. Based on these data, we propose that the Sprouty proteins are involved normally in mediating the sexually dimorphic signaling of FGF9 and controlling cell migration from the mesonephros during testis development.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3-Hydroxysteroid Dehydrogenases / genetics
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Cell Movement / physiology
-
Endothelial Cells / physiology
-
Extracellular Signal-Regulated MAP Kinases / metabolism
-
Female
-
Fibroblast Growth Factor 9 / genetics*
-
Fibroblast Growth Factor 9 / metabolism
-
Gene Expression Regulation, Developmental*
-
Homeodomain Proteins / genetics
-
Intracellular Signaling Peptides and Proteins
-
LIM-Homeodomain Proteins
-
Laminin / genetics
-
Leydig Cells / physiology
-
Male
-
Membrane Proteins
-
Mesonephros / cytology
-
Mesonephros / embryology
-
Mesonephros / physiology
-
Mice
-
Mice, Inbred Strains
-
Mice, Transgenic
-
Myocytes, Smooth Muscle / physiology
-
Organ Culture Techniques
-
PAX2 Transcription Factor / genetics
-
Pregnancy
-
Promoter Regions, Genetic / physiology
-
Protein Serine-Threonine Kinases
-
Proteins / genetics
-
Proteins / metabolism*
-
Proto-Oncogene Proteins / genetics
-
Sex Differentiation / physiology
-
Testis / cytology
-
Testis / embryology*
-
Testis / physiology*
-
Transcription Factors
-
Wnt Proteins / genetics
-
Wnt4 Protein
-
Wolffian Ducts / cytology
-
Wolffian Ducts / embryology
-
Wolffian Ducts / physiology
Substances
-
Adaptor Proteins, Signal Transducing
-
Fgf9 protein, mouse
-
Fibroblast Growth Factor 9
-
Homeodomain Proteins
-
Intracellular Signaling Peptides and Proteins
-
LIM-Homeodomain Proteins
-
Laminin
-
Lhx1 protein, mouse
-
Membrane Proteins
-
PAX2 Transcription Factor
-
Pax2 protein, mouse
-
Proteins
-
Proto-Oncogene Proteins
-
Transcription Factors
-
Wnt Proteins
-
Wnt4 Protein
-
Wnt4 protein, mouse
-
Wnt7a protein, mouse
-
3-Hydroxysteroid Dehydrogenases
-
Protein Serine-Threonine Kinases
-
Spry2 protein, mouse
-
Extracellular Signal-Regulated MAP Kinases