Published ahead of print on December 1, 2006, doi:10.1165/rcmb.2006-0211RC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 4, April 2007, 391-397 A more recent version of this article appeared on April 1, 2007
Submitted on June 12, 2006 Gata4 is Necessary for Normal Pulmonary Lobar DevelopmentKate G Ackerman1*,1 Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Division of Emergency Medicine, Children's Hopsital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA, 2 Harvard Medical School, Boston, MA, USA; Division of Hematology and Oncology, Children's Hospital, Boston, MA, USA, 3 Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA, 4 Harvard Medical School, Boston, MA, USA; Division of Hematology and Oncology, Children's Hospital, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA, 5 Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA * To whom correspondence should be addressed. E-mail: kackerman{at}rics.bwh.harvard.edu.
Mutations of Fog2 in mice result in a phenotype that includes pulmonary lobar defects. To determine whether formation of the accessory lobe bronchus is mediated by a Gata family cofactor, we evaluated embryonic lungs from mice carrying missense mutations that cause loss of FOG-GATA protein interaction. Lungs from embryos carrying a missense mutation in Gata6 were structurally normal, while lungs from embryos carrying mutations of either Gata4 or of both Gata4 and Gata6 had a structural phenotype that matched the Fog2 mutant phenotype. Expression analysis showed that Gata4 and Fog2 are expressed in the ventral and medial pulmonary mesenchyme during secondary budding. Although Gata4 has not previously been suspected as playing a role in lung development, we have found that a Fog2-Gata4 interaction is critical for the development of normal pulmonary lobar structure, and this phenotype is not influenced by the additional loss of Gata6 interaction. Fog2 and Gata4 in the early pulmonary mesenchyme participate in patterning the secondary bronchus of the accessory lobe.
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