FGF9 suppresses meiosis and promotes male germ cell fate in mice.
Sex determination of mammalian germ cells occurs during fetal development and depends on signals from gonadal somatic cells. Previous studies have established that retinoic acid (RA) triggers ovarian germ cells to enter meiosis and thereby commit to oogenesis, whereas in the developing testis, the enzyme CYP26B1 degrades RA and germ cells are not induced to enter meiosis. Using in vitro and in vivo models, we demonstrate that fibroblast growth factor 9 (FGF9) produced in the fetal testis acts directly on germ cells to inhibit meiosis; in addition, FGF9 maintains expression of pluripotency-related genes and upregulates markers associated with male germ cell fate. We conclude that two independent and mutually antagonistic pathways involving RA and FGF9 act in concert to determine mammalian germ cell sexual fate commitment and support a model in which the mitosis/meiosis switch is robustly controlled by both positive and negative regulatory factors.
Bowles
Josephine
J
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Feng
Chun-Wei
CW
Spiller
Cassy
C
Davidson
Tara-Lynne
TL
Jackson
Andrew
A
Koopman
Peter
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051525:Fibroblast Growth Factor 9 / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005854:Germ Cells / Q000502:physiology*; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009866:Oogenesis / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000196:embryology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013737:Testis / Q000196:embryology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D012333:RNA, Messenger; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase