Foxp transcription factors suppress a non-pulmonary gene expression program to 
permit proper lung development

Li, Shanru; Morley, Michael; Lu, MinMin; Zhou, Su; Stewart, Kathleen; French, Catherine A.; Tucker , Haley O.; Fisher, Simon E.; Morrisey, Edward E.

doi:10.1016/j.ydbio.2016.06.020

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Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development

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Fisher, Simon E.
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

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Citation

Li, S., Morley, M., Lu, M., Zhou, S., Stewart, K., French, C. A., et al. (2016). Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development. Developmental Biology, 416(2), 338-346. doi:10.1016/j.ydbio.2016.06.020.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002A-F4BE-7

Abstract

The inhibitory mechanisms that prevent gene expression programs from one tissue to be expressed in another are poorly understood. Foxp1/2/4 are forkhead transcription factors that repress gene expression and are individually important for endoderm development. We show that combined loss of all three Foxp1/2/4 family members in the developing anterior foregut endoderm leads to a loss of lung endoderm lineage commitment and subsequent development. Foxp1/2/4 deficient lungs express high levels of transcriptional regulators not normally expressed in the developing lung, including Pax2, Pax8, Pax9 and the Hoxa9-13 cluster. Ectopic expression of these transcriptional regulators is accompanied by decreased expression of lung restricted transcription factors including Nkx2-1, Sox2, and Sox9. Foxp1 binds to conserved forkhead DNA binding sites within the Hoxa9-13 cluster, indicating a direct repression mechanism. Thus, Foxp1/2/4 are essential for promoting lung endoderm development by repressing expression of non-pulmonary transcription factors