Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice

Spiller, Cassy M., Wilhelm, Dagmar and Koopman, Peter (2010) Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice. Biology of Reproduction, 82 2: 433-443. doi:10.1095/biolreprod.109.078691


Author Spiller, Cassy M.
Wilhelm, Dagmar
Koopman, Peter
Title Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice
Formatted title
Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
1529-7268
Publication date 2010-02-01
Year available 2009
Sub-type Article (original research)
DOI 10.1095/biolreprod.109.078691
Open Access Status Not yet assessed
Volume 82
Issue 2
Start page 433
End page 443
Total pages 11
Editor John J. Eppig
Place of publication Madison, WI, U.S.A.
Publisher Society for the Study of Reproduction
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract During mouse germ cell development, the first sign of sex differentiation occurs when XY germ cells enter G1/G0 arrest from 12.5 days postcoitum (dpc). Retinoblastoma 1 (RB1), a potent cell cycle regulator, was investigated in XY germ cell arrest by studying germ cell proliferation in Rb1−/− mutant mouse embryos. Because mice homozygous for the Rb1 deletion die in utero around 14.5 dpc, we used ex vivo culture techniques to allow analysis of developing gonads to 16.5 dpc. In Rb1−/− gonads, we observed normal somatic cell development, assessed by immunofluorescence for markers HSD3B1 and anti-Müllerian hormone. However, at 14.5 dpc, when wild-type XY germ cells had arrested, we could detect actively proliferating germ cells using the proliferation markers MKI67, pHH3, and bromodeoxyuridine incorporation. The increased proliferation was reflected with a trend of increased germ cell number and expression of germ cell markers Ddx4 and Pou5f1 in the Rb1−/− testes. By 16.5 dpc, this phenotype was resolved such that the entire germ cell population had entered G1/G0 arrest, although the total germ cell number remained elevated. At each stage analyzed, we saw no increase in expression of RB1 family members Rbl1 and Rbl2 in the Rb1−/− testes, but we saw a significant increase of cyclin-dependent kinase (CDK) inhibitor Cdkn1b and Cdkn2b expression. We conclude that Rb1 is required for correct germ cell entry into G1/G0 arrest in the wild-type gonad at 14.5 dpc, but in its absence, upregulation of other cell cycle suppressors, including Cdkn1b and Cdkn2b, can induce delayed germ cell arrest.
Keyword Cell cycle
Developmental biology
Fetal testis
G(1)/G(0) arrest
Gametogenesis
Germ cell
Mouse
Retinoblastoma 1
Testis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print October 28, 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 07 Feb 2010, 10:08:36 EST