Endogenous nodal signaling regulates germ cell potency during mammalian testis development

Spiller, Cassy M., Feng, Chun-Wei, Jackson, Andrew, Gillis, Ad J. M., Rolland, Antoine D., Looijenga, Leendert H. J., Koopman, Peter and Bowles, Josephine (2012) Endogenous nodal signaling regulates germ cell potency during mammalian testis development. Development, 139 22: 4123-4132. doi:10.1242/dev.083006

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Author Spiller, Cassy M.
Feng, Chun-Wei
Jackson, Andrew
Gillis, Ad J. M.
Rolland, Antoine D.
Looijenga, Leendert H. J.
Koopman, Peter
Bowles, Josephine
Title Endogenous nodal signaling regulates germ cell potency during mammalian testis development
Journal name Development   Check publisher's open access policy
ISSN 0950-1991
1477-9129
Publication date 2012-10-03
Year available 2012
Sub-type Article (original research)
DOI 10.1242/dev.083006
Open Access Status File (Publisher version)
Volume 139
Issue 22
Start page 4123
End page 4132
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Abstract Germ cells, the embryonic precursors of sperm or oocytes, respond to molecular cues that regulate their sex-specific development in the fetal gonads. In males in particular, the balance between continued proliferation and cell fate commitment is crucial: defects in proliferation result in insufficient spermatogonial stem cells for fertility, but escape from commitment and prolonged pluripotency can cause testicular germ cell tumors. However, the factors that regulate this balance remain unidentified. Here, we show that signaling by the TGF beta morphogen Nodal and its co-receptor Cripto is active during a crucial window of male germ cell development. The Nodal pathway is triggered when somatic signals, including FGF9, induce testicular germ cells to upregulate Cripto. Germ cells of mutant mice with compromised Nodal signaling showed premature differentiation, reduced pluripotency marker expression and a reduced ability to form embryonic germ (EG) cell colonies in vitro. Conversely, human testicular tumors showed upregulation of NODAL and CRIPTO that was proportional to invasiveness and to the number of malignant cells. Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer.
Formatted abstract
Germ cells, the embryonic precursors of sperm or oocytes, respond to molecular cues that regulate their sex-specific development in the fetal gonads. In males in particular, the balance between continued proliferation and cell fate commitment is crucial: defects in proliferation result in insufficient spermatogonial stem cells for fertility, but escape from commitment and prolonged pluripotency can cause testicular germ cell tumors. However, the factors that regulate this balance remain unidentified. Here, we show that signaling by the TGFβ morphogen Nodal and its co-receptor Cripto is active during a crucial window of male germ cell development. The Nodal pathway is triggered when somatic signals, including FGF9, induce testicular germ cells to upregulate Cripto. Germ cells of mutant mice with compromised Nodal signaling showed premature differentiation, reduced pluripotency marker expression and a reduced ability to form embryonic germ (EG) cell colonies in vitro. Conversely, human testicular tumors showed upregulation of NODAL and CRIPTO that was proportional to invasiveness and to the number of malignant cells. Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer
Keyword Germ cell
Mouse
Nodal
Pluripotency
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1030146
DP110105459
APP1012325
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 16 Nov 2012, 23:45:51 EST by Susan Allen on behalf of Institute for Molecular Bioscience