|
Originally published In Press as doi:10.1074/jbc.M403212200 on May 6, 2004
J. Biol. Chem., Vol. 279, Issue 31, 32281-32286, July 30, 2004
Growth Differentiation Factor 9 Regulates Expression of the Bone Morphogenetic Protein Antagonist Gremlin*
Stephanie A. Pangas  ,
Carolina J. Jorgez¶, and
Martin M. Matzuk||**
From the
Departments of Pathology, Molecular and Cellular Biology, and ||Molecular and Human Genetics and ¶Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030
Growth differentiation factor 9 (GDF9) is an oocyte-expressed member of the transforming growth factor  (TGF-) superfamily and is required for normal ovarian follicle development and female fertility. GDF9 acts as a paracrine factor and affects granulosa cell physiology. Only a few genes regulated by GDF9 are known. Our microarray analysis has identified gremlin as one of the genes up-regulated by GDF9 in cultures of granulosa cells. Gremlin is a known member of the DAN family of bone morphogenetic protein (BMP) antagonists, but its expression and function in the ovary are unknown. We have investigated the regulation of gremlin in mouse granulosa cells by GDF9 as well as other members of the TGF- superfamily. GDF9 and BMP4 induce gremlin, but TGF- does not. In addition, in cultures of granulosa cells, gremlin negatively regulates BMP4 signaling but not GDF9 activity. The expression of gremlin in the ovary was also examined by in situ hybridization. A distinct change in gremlin mRNA compartmentalization occurs during follicle development and ovulation, indicating a highly regulated expression pattern during folliculogenesis. We propose that gremlin modulates the cross-talk between GDF9 and BMP signaling that is necessary during follicle development because both ligands use components of the same signaling pathway.
Received for publication, March 23, 2004
, and in revised form, May 4, 2004.
* These studies were supported by National Institutes of Health Grants HD32067 and HD33438 (to M. M. M.) and a postdoctoral fellowship from the Center for Reproductive Biology (Training Grant HD007165 to S. A. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
** Stuart A. Wallace Chair and Professor. To whom correspondence should be addressed: Dept. of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Tel.: 713-798-6451; Fax: 713-798-5833; E-mail: mmatzuk{at}bcm.tmc.edu.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. N. Harvey, M. Esmail, Q. Wang, A. I. Brooks, R. Zachow, and M. Uzumcu
Effect of the Methoxychlor Metabolite HPTE on the Rat Ovarian Granulosa Cell Transcriptome In Vitro
Toxicol. Sci.,
July 1, 2009;
110(1):
95 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Li, S. A. Pangas, C. J. Jorgez, J. M. Graff, M. Weinstein, and M. M. Matzuk
Redundant Roles of SMAD2 and SMAD3 in Ovarian Granulosa Cells In Vivo
Mol. Cell. Biol.,
December 1, 2008;
28(23):
7001 - 7011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Li, L. J. McKenzie, and M. M. Matzuk
Revisiting oocyte-somatic cell interactions: in search of novel intrafollicular predictors and regulators of oocyte developmental competence
Mol. Hum. Reprod.,
December 1, 2008;
14(12):
673 - 678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Assidi, I. Dufort, A. Ali, M. Hamel, O. Algriany, S. Dielemann, and M.-A. Sirard
Identification of Potential Markers of Oocyte Competence Expressed in Bovine Cumulus Cells Matured with Follicle-Stimulating Hormone and/or Phorbol Myristate Acetate In Vitro
Biol Reprod,
August 1, 2008;
79(2):
209 - 222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Pangas, X. Li, L. Umans, A. Zwijsen, D. Huylebroeck, C. Gutierrez, D. Wang, J. F. Martin, S. P. Jamin, R. R. Behringer, et al.
Conditional Deletion of Smad1 and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice
Mol. Cell. Biol.,
January 1, 2008;
28(1):
248 - 257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Cillo, T. A L Brevini, S. Antonini, A. Paffoni, G. Ragni, and F. Gandolfi
Association between human oocyte developmental competence and expression levels of some cumulus genes
Reproduction,
November 1, 2007;
134(5):
645 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Clelland, Q. Tan, A. Balofsky, R. Lacivita, and C. Peng
Inhibition of Premature Oocyte Maturation: A Role for Bone Morphogenetic Protein 15 in Zebrafish Ovarian Follicles
Endocrinology,
November 1, 2007;
148(11):
5451 - 5458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Pangas, C. J. Jorgez, M. Tran, J. Agno, X. Li, C. W. Brown, T. R. Kumar, and M. M. Matzuk
Intraovarian Activins Are Required for Female Fertility
Mol. Endocrinol.,
October 1, 2007;
21(10):
2458 - 2471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Andreu-Vieyra, R. Chen, and M. M. Matzuk
Effects of Granulosa Cell-Specific Deletion of Rb in Inha-{alpha} Null Female Mice
Endocrinology,
August 1, 2007;
148(8):
3837 - 3849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Russell and R. L. Robker
Molecular mechanisms of ovulation: co-ordination through the cumulus complex
Hum. Reprod. Update,
May 1, 2007;
13(3):
289 - 312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G Knight and C. Glister
TGF-{beta} superfamily members and ovarian follicle development.
Reproduction,
August 1, 2006;
132(2):
191 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mazerbourg and A. J.W. Hsueh
Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands
Hum. Reprod. Update,
July 1, 2006;
12(4):
373 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Pangas, X. Li, E. J. Robertson, and M. M. Matzuk
Premature Luteinization and Cumulus Cell Defects in Ovarian-Specific Smad4 Knockout Mice
Mol. Endocrinol.,
June 1, 2006;
20(6):
1406 - 1422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Moll, C. Millet, D. Noel, B. Orsetti, A. Bardin, D. Katsaros, C. Jorgensen, M. Garcia, C. Theillet, P. Pujol, et al.
Chordin is underexpressed in ovarian tumors and reduces tumor cell motility
FASEB J,
February 1, 2006;
20(2):
240 - 250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Lacham-Kaplan, H. Chy, and A. Trounson
Testicular Cell Conditioned Medium Supports Differentiation of Embryonic Stem Cells into Ovarian Structures Containing Oocytes
Stem Cells,
February 1, 2006;
24(2):
266 - 273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Clelland, G. Kohli, R. K. Campbell, S. Sharma, S. Shimasaki, and C. Peng
Bone Morphogenetic Protein-15 in the Zebrafish Ovary: Complementary Deoxyribonucleic Acid Cloning, Genomic Organization, Tissue Distribution, and Role in Oocyte Maturation
Endocrinology,
January 1, 2006;
147(1):
201 - 209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Hussein, D. A. Froiland, F. Amato, J. G. Thompson, and R. B. Gilchrist
Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins
J. Cell Sci.,
November 15, 2005;
118(22):
5257 - 5268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Pangas and M. M. Matzuk
The Art and Artifact of GDF9 Activity: Cumulus Expansion and the Cumulus Expansion-Enabling Factor
Biol Reprod,
October 1, 2005;
73(4):
582 - 585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Glister, S. L. Richards, and P. G. Knight
Bone Morphogenetic Proteins (BMP) -4, -6, and -7 Potently Suppress Basal and Luteinizing Hormone-Induced Androgen Production by Bovine Theca Interna Cells in Primary Culture: Could Ovarian Hyperandrogenic Dysfunction Be Caused by a Defect in Thecal BMP Signaling?
Endocrinology,
April 1, 2005;
146(4):
1883 - 1892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.L. Juengel and K.P. McNatty
The role of proteins of the transforming growth factor-{beta} superfamily in the intraovarian regulation of follicular development
Hum. Reprod. Update,
March 1, 2005;
11(2):
144 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Thomas, J.-F. Ethier, S. Shimasaki, and B. C. Vanderhyden
Follicle-Stimulating Hormone Regulates Oocyte Growth by Modulation of Expression of Oocyte and Granulosa Cell Factors
Endocrinology,
February 1, 2005;
146(2):
941 - 949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.J. McKenzie, S.A. Pangas, S.A. Carson, E. Kovanci, P. Cisneros, J.E. Buster, P. Amato, and M.M. Matzuk
Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF
Hum. Reprod.,
December 1, 2004;
19(12):
2869 - 2874.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|
