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

Abstract

ABSTRACT 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.