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Molecular and Cellular Biology, January 2005, p. 685-698, Vol. 25, No. 2
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.2.685-698.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Transcription Factor Gene Nfib Is Essential for both Lung Maturation and Brain Development

George Steele-Perkins,1,{dagger} Céline Plachez,2 Kenneth G. Butz,1 Guanhu Yang,3 Cindy J. Bachurski,3 Stephen L. Kinsman,4 E. David Litwack,2 Linda J. Richards,2 and Richard M. Gronostajski1*

Department of Biochemistry and the Program in Neuroscience, State University of New York at Buffalo, Buffalo, New York,1 Division of Pulmonary Biology, Cincinnati Children's Research Foundation, Cincinnati, Ohio,3 Department of Anatomy and Neurobiology and Program in Neuroscience,2 Department of Pediatrics, University of Maryland, Baltimore, School of Medicine, Baltimore, Maryland4

Received 25 September 2004/ Accepted 10 October 2004

The phylogenetically conserved nuclear factor I (NFI) gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects, whereas Nfic-deficient mice have agenesis of molar tooth roots and severe incisor defects. Here we show that Nfib-deficient mice possess unique defects in lung maturation and exhibit callosal agenesis and forebrain defects that are similar to, but more severe than, those seen in Nfia-deficient animals. In addition, loss of Nfib results in defects in basilar pons formation and hippocampus development that are not seen in Nfia-deficient mice. Heterozygous Nfib-deficient animals also exhibit callosal agenesis and delayed lung maturation, indicating haploinsufficiency at the Nfib locus. The similarity in brain defects in Nfia- and Nfib-deficient animals suggests that these two genes may cooperate in late fetal forebrain development, while Nfib is essential for late fetal lung maturation and development of the pons.

* Corresponding author. Mailing address: State University of New York at Buffalo, Dept. of Biochemistry, 140 Farber Hall, 3435 Main St., Buffalo, NY 14214-3000. Phone: (716) 829-3471. Fax: (716) 829-2725. E-mail: rgron{at}buffalo.edu.

{dagger} Present address: Buffalo, NY 14215.

Molecular and Cellular Biology, January 2005, p. 685-698, Vol. 25, No. 2
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.2.685-698.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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