Retinoid signaling determines germ cell fate in mice.
Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and initiate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.
Division of Genetics and Developmental Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Josephine
J
Bowles
Deon
D
Knight
Christopher
C
Smith
Dagmar
D
Wilhelm
Joy
J
Richman
Satoru
S
Mamiya
Kenta
K
Yashiro
Kallayanee
K
Chawengsaksophak
Megan J
MJ
Wilson
Janet
J
Rossant
Hiroshi
H
Hamada
Peter
P
Koopman
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005854:Germ Cells / Q000502:physiology*; D017403:In Situ Hybridization; D007763:Lac Operon; D008297:Male; D008540:Meiosis; D008650:Mesonephros / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009281:Naphthalenes / Q000494:pharmacology; D009866:Oogenesis; D010053:Ovary / Q000196:embryology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D000072516:Retinoic Acid 4-Hydroxylase; D012708:Sertoli Cells / Q000201:enzymology; D012727:Sex Characteristics; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000196:embryology / Q000378:metabolism; D046509:Tissue Culture Techniques; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D009281:Naphthalenes; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C096920:AGN 193109