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Molecular and Cellular Biology, July 2001, p. 4391-4398, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4391-4398.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Nkx2.5 and Nkx2.6, Homologs of Drosophila tinman, Are Required for Development of the Pharynx

Makoto Tanaka,dagger Martina Schinke, Hai-Sun Liao, Naohito Yamasaki, and Seigo Izumo*

Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215

Received 22 January 2001/Returned for modification 1 March 2001/Accepted 23 March 2001

Nkx2.5 and Nkx2.6 are murine homologs of Drosophila tinman. Their genes are expressed in the ventral region of the pharynx at early stages of embryogenesis. However, no abnormalities in the pharynges of embryos with mutations in either Nkx2.5 or Nkx2.6 have been reported. To examine the function of Nkx2.5 and Nkx2.6 in the formation of the pharynx, we generated and analyzed Nkx2.5 and Nkx2.6 double-mutant mice. Interestingly, in the double-mutant embryos, the pharynx did not form properly. Pharyngeal endodermal cells were largely missing, and the mutant pharynx was markedly dilated. Moreover, we observed enhanced apoptosis and reduced proliferation in pharyngeal endodermal cells of the double-mutant embryos. These results demonstrated a critical role of the NK-2 homeobox genes in the differentiation, proliferation, and survival of pharyngeal endodermal cells. Furthermore, the development of the atrium was less advanced in the double-mutant embryos, indicating that these two genes are essential for both pharyngeal and cardiac development.

* Corresponding author. Mailing address: SL-201, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. Phone: (617) 667-4858. Fax: (617) 975-5268. E-mail: sizumo{at}caregroup.harvard.edu.

dagger Present address: Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Molecular and Cellular Biology, July 2001, p. 4391-4398, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4391-4398.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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