A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice

Ewen, Katherine, Jackson, Andrew, Wilhelm, Dagmar and Koopman, Peter (2010) A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice. Biology of Reproduction, 83 6: 1005-1014. doi:10.1095/biolreprod.110.086801


Author Ewen, Katherine
Jackson, Andrew
Wilhelm, Dagmar
Koopman, Peter
Title A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice
Formatted title
A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice1
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
1529-7268
0523-6754
Publication date 2010-12-01
Year available 2010
Sub-type Article (original research)
DOI 10.1095/biolreprod.110.086801
Open Access Status
Volume 83
Issue 6
Start page 1005
End page 1014
Total pages 10
Editor Bernard Robaire
Bruce D. Murphy
Place of publication Madison, WI, U.S.A.
Publisher Society for the Study of Reproduction
Language eng
Abstract Germ cell sex differentialion 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 p:38 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.
Formatted abstract
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.
© 2010 by the Society for the Study of Reproduction, Inc.
Keyword Developmental biology
Differentiation
Germ cell
Kinases
Meiosis
Mitotic arrest
Testis
p38 MAPK
Transcriptional repressor Hbp1
Signal-transduction pathway
MAP kinase
c-Myc
Retinoic acid
Mouse gonads
Chromosome synapsis
Reduced fertility
Tumor suppression
Gene-expression
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 19 Dec 2010, 10:15:36 EST