A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice.
Germ cell sex differentiation in the mouse embryo is denoted by meiosis entry in females and mitotic arrest in males. Because p38 mitogen-activated protein kinase (MAPK) signaling initiates mitotic arrest in other differentiating cell types, we investigated its potential role in XY germ cell differentiation in mice. We report that p38 MAPK is phosphorylated and therefore activated only in XY germ cells around the time of sex differentiation. Quantitative RT-PCR analysis showed that 14 known targets of p38 MAPK signaling are expressed in the embryonic gonads at this time and that five of these targets (Mapkapk5, Max, Myc, Hbp1, and Cebpa) have expression profiles similar to that of activated p38 MAPK. Inhibition of p38 MAPK signaling in XY germ cells ex vivo reduced expression of the pluripotency marker POU5F1 and increased the expression of Stra8 and SYCP3, premeiosis and meiosis markers, respectively, to levels approaching those observed in XX germ cells. These data suggest that p38 MAPK signaling antagonizes entry into meiosis in XY germ cells, instead directing them toward mitotic quiescence and a spermatogenic fate.
Ewen
Katherine
K
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Jackson
Andrew
A
Wilhelm
Dagmar
D
Koopman
Peter
P
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000378:metabolism*; D006066:Gonads / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; C486329:Hbp1 protein, mouse; D006609:High Mobility Group Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D012097:Repressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases