This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chung, A. C.-K.
Right arrow Articles by O'Malley, B. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chung, A. C.-K.
Right arrow Articles by O'Malley, B. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2001, p. 663-677, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.663-677.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Loss of Orphan Receptor Germ Cell Nuclear Factor Function Results in Ectopic Development of the Tail Bud and a Novel Posterior Truncation

Arthur C.-K. Chung, Deborah Katz, Fred A. Pereira, Kathy J. Jackson, Francesco J. DeMayo, Austin J. Cooney,* and Bert W. O'Malley

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Received 30 August 2000/Returned for modification 13 October 2000/Accepted 26 October 2000

The dynamic embryonic expression of germ cell nuclear factor (GCNF), an orphan nuclear receptor, suggests that it may play an important role during early development. To determine the physiological role of GCNF, we have generated a targeted mutation of the GCNF gene in mice. Germ line mutation of the GCNF gene proves that the orphan nuclear receptor is essential for embryonic survival and normal development. GCNF-/- embryos cannot survive beyond 10.5 days postcoitum (dpc), probably due to cardiovascular failure. Prior to death, GCNF-/- embryos suffer significant defects in posterior development. Unlike GCNF+/+ embryos, GCNF-/- embryos do not turn and remain in a lordotic position, the majority of the neural tube remains open, and the hindgut fails to close. GCNF-/- embryos also suffer serious defects in trunk development, specifically in somitogenesis, which terminates by 8.75 dpc. The maximum number of somites in GCNF-/- embryos is 13 instead of 25 as in the GCNF+/+ embryos. Interestingly, the tailbud of GCNF-/- embryos develops ectopically outside the yolk sac. Indeed, alterations in expression of multiple marker genes were identified in the posterior of GCNF-/- embryos, including the primitive streak, the node, and the presomitic mesoderm. These results suggest that GCNF is required for maintenance of somitogenesis and posterior development and is essential for embryonic survival. These results suggest that GCNF regulates a novel and critical developmental pathway involved in normal anteroposterior development.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6250. Fax: (713) 790-1275. E-mail: acooney{at}bcm.tmc.edu.

Molecular and Cellular Biology, January 2001, p. 663-677, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.663-677.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wilson, V., Olivera-Martinez, I., Storey, K. G. (2009). Stem cells, signals and vertebrate body axis extension. Development 136: 1591-1604 [Abstract] [Full Text]  
  • Lan, Z.-J., Xu, X., Chung, A. C.-K., Cooney, A. J. (2009). Extra-Germ Cell Expression of Mouse Nuclear Receptor Subfamily 6, Group A, Member 1 (NR6A1). Biol. Reprod. 80: 905-912 [Abstract] [Full Text]  
  • Akamatsu, W., DeVeale, B., Okano, H., Cooney, A. J, van der Kooy, D. (2009). Suppression of Oct4 by Germ Cell Nuclear Factor Restricts Pluripotency and Promotes Neural Stem Cell Development in the Early Neural Lineage. J. Neurosci. 29: 2113-2124 [Abstract] [Full Text]  
  • Sun, Q.-Y., Liu, K., Kikuchi, K. (2008). Oocyte-Specific Knockout: A Novel In Vivo Approach for Studying Gene Functions During Folliculogenesis, Oocyte Maturation, Fertilization, and Embryogenesis. Biol. Reprod. 79: 1014-1020 [Abstract] [Full Text]  
  • Mikawa, S., Morozumi, T., Shimanuki, S.-I., Hayashi, T., Uenishi, H., Domukai, M., Okumura, N., Awata, T. (2007). Fine mapping of a swine quantitative trait locus for number of vertebrae and analysis of an orphan nuclear receptor, germ cell nuclear factor (NR6A1). Genome Res 17: 586-593 [Abstract] [Full Text]  
  • Gu, P., Le Menuet, D., Chung, A. C.-K., Cooney, A. J. (2006). Differential Recruitment of Methylated CpG Binding Domains by the Orphan Receptor GCNF Initiates the Repression and Silencing of Oct4 Expression. Mol. Cell. Biol. 26: 9471-9483 [Abstract] [Full Text]  
  • Benoit, G., Cooney, A., Giguere, V., Ingraham, H., Lazar, M., Muscat, G., Perlmann, T., Renaud, J.-P., Schwabe, J., Sladek, F., Tsai, M.-J., Laudet, V. (2006). International Union of Pharmacology. LXVI. Orphan Nuclear Receptors. Pharmacol. Rev. 58: 798-836 [Abstract] [Full Text]  
  • Hentschke, M., Kurth, I., Borgmeyer, U., Hubner, C. A. (2006). Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3. J. Biol. Chem. 281: 33497-33504 [Abstract] [Full Text]  
  • Juric, D., Sale, S., Hromas, R. A., Yu, R., Wang, Y., Duran, G. E., Tibshirani, R., Einhorn, L. H., Sikic, B. I. (2005). Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures. Proc. Natl. Acad. Sci. USA 102: 17763-17768 [Abstract] [Full Text]  
  • (2005). Genetically Modified Animals in Endocrinology. Endocr. Rev. 26: 985-993 [Abstract] [Full Text]  
  • Gu, P., LeMenuet, D., Chung, A. C.-K., Mancini, M., Wheeler, D. A., Cooney, A. J. (2005). Orphan Nuclear Receptor GCNF Is Required for the Repression of Pluripotency Genes during Retinoic Acid-Induced Embryonic Stem Cell Differentiation. Mol. Cell. Biol. 25: 8507-8519 [Abstract] [Full Text]  
  • Gu, P., Goodwin, B., Chung, A. C.-K., Xu, X., Wheeler, D. A., Price, R. R., Galardi, C., Peng, L., Latour, A. M., Koller, B. H., Gossen, J., Kliewer, S. A., Cooney, A. J. (2005). Orphan Nuclear Receptor LRH-1 Is Required To Maintain Oct4 Expression at the Epiblast Stage of Embryonic Development. Mol. Cell. Biol. 25: 3492-3505 [Abstract] [Full Text]  
  • Rajkovic, M., Middendorff, R., Wetzel, M. G., Frkovic, D., Damerow, S., Seitz, H. J., Weitzel, J. M. (2004). Germ Cell Nuclear Factor Relieves cAMP-response Element Modulator {tau}-mediated Activation of the Testis-specific Promoter of Human Mitochondrial Glycerol-3-phosphate Dehydrogenase. J. Biol. Chem. 279: 52493-52499 [Abstract] [Full Text]  
  • Sattler, U., Samochocki, M., Maelicke, A., Zechel, C. (2004). The Expression Level of the Orphan Nuclear Receptor GCNF (Germ Cell Nuclear Factor) Is Critical for Neuronal Differentiation. Mol. Endocrinol. 18: 2714-2726 [Abstract] [Full Text]  
  • Lan, Z.-J., Xu, X., Cooney, A. J. (2004). Differential Oocyte-Specific Expression of Cre Recombinase Activity in GDF-9-iCre, Zp3cre, and Msx2Cre Transgenic Mice. Biol. Reprod. 71: 1469-1474 [Abstract] [Full Text]  
  • Yang, G., Zhang, Y.-L., Buchold, G. M., Jetten, A. M., O'Brien, D. A. (2003). Analysis of Germ Cell Nuclear Factor Transcripts and Protein Expression During Spermatogenesis. Biol. Reprod. 68: 1620-1630 [Abstract] [Full Text]  
  • Hu, Y., Zhou, Z., Xu, C., Shang, Q., Zhang, Y.-D., Zhang, Y.-L. (2003). Androgen Down-Regulated and Region-Specific Expression of Germ Cell Nuclear Factor in Mouse Epididymis. Endocrinology 144: 1612-1619 [Abstract] [Full Text]  
  • Lan, Z.-J., Gu, P., Xu, X., Cooney, A. J. (2003). Expression of the Orphan Nuclear Receptor, Germ Cell Nuclear Factor, in Mouse Gonads and Preimplantation Embryos. Biol. Reprod. 68: 282-289 [Abstract] [Full Text]  
  • Lan, Z.-J., Chung, A. C.-K., Xu, X., DeMayo, F. J., Cooney, A. J. (2002). The Embryonic Function of Germ Cell Nuclear Factor Is Dependent on the DNA Binding Domain. J. Biol. Chem. 277: 50660-50667 [Abstract] [Full Text]  
  • Yan, Z., Kim, Y.-S., Jetten, A. M. (2002). RAP80, a Novel Nuclear Protein That Interacts with the Retinoid-related Testis-associated Receptor. J. Biol. Chem. 277: 32379-32388 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»