Foxp2 and Foxp1 cooperatively regulate lung and esophagus development
Author:
Shu Weiguo1, Lu Min Min1, Zhang Yuzhen1, Tucker Philip W.2, Zhou Deying1, Morrisey Edward E.13
Affiliation:
1. Cardiovascular Institute, University of Pennsylvania, 956 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA. 2. Department of Molecular Genetics and the Institute for Cellular and Molecular Biology, University of Texas at Austin, TX, USA. 3. Department of Cell and Developmental Biology, University of Pennsylvania, 956 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Abstract
The airways of the lung develop through a reiterative process of branching morphogenesis that gives rise to the intricate and extensive surface area required for postnatal respiration. The forkhead transcription factors Foxp2 and Foxp1 are expressed in multiple foregut-derived tissues including the lung and intestine. In this report, we show that loss of Foxp2 in mouse leads to defective postnatal lung alveolarization, contributing to postnatal lethality. Using in vitro and in vivo assays, we show that T1alpha, a lung alveolar epithelial type 1 cell-restricted gene crucial for lung development and function, is a direct target of Foxp2 and Foxp1. Remarkably, loss of a single Foxp1 allele in addition to complete loss of Foxp2 results in increased severity of morphological defects in mutant lungs and leads to perinatal loss of all Foxp2-/-;Foxp1+/- mice. Expression of N-myc and Hop, crucial regulators of lung development, is compromised in Foxp2-/-;Foxp1+/- mutants. In addition to the defects in lung development, esophageal muscle development is disrupted in Foxp2-/-;Foxp1+/- embryos, a tissue where Foxp2 and Foxp1 are co-expressed. These data identify Foxp2 and Foxp1 as crucial regulators of lung and esophageal development, underscoring the necessity of these transcription factors in the development of anterior foregut-derived tissues and demonstrating functional cooperativity between members of the Foxp1/2/4 family in tissues where they are co-expressed.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference31 articles.
1. Banham, A. H., Beasley, N., Campo, E., Fernandez, P. L., Fidler,C., Gatter, K., Jones, M., Mason, D. Y., Prime, J. E., Trougouboff, P. et al. (2001). The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res.61,8820-8829. 2. Bellusci, S., Furuta, Y., Rush, M. G., Henderson, R., Winnier,G. and Hogan, B. L. (1997). Involvement of Sonic hedgehog(Shh) in mouse embryonic lung growth and morphogenesis. Development124,53-63. 3. Besnard, V., Wert, S. E., Kaestner, K. H. and Whitsett, J. A. (2005). Stage-specific regulation of respiratory epithelial cell differentiation by Foxa1. Am. J. Physiol. Lung Cell. Mol. Physiol.289,L750-L759. 4. Cardoso, W. V. and Lu, J. (2006). Regulation of early lung morphogenesis: questions, facts and controversies. Development133,1611-1624. 5. Girod, C. E., Shin, D. H., Geraci, M. W., Warren, H. B., Dobbs,L. G., Gao, B., Rainer, J. S., Bauer, A. K., Ikegami, M., Shannon, J. M. et al. (1999). Surfactant protein C promoter-driven expression of T1-alpha induces lung inflammation. Chest116, 61S.
Cited by
259 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|