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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.



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