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

Dev Biol. 2016 Aug 15;416(2):338-46. doi: 10.1016/j.ydbio.2016.06.020. Epub 2016 Jun 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Conserved Sequence
  • DNA / genetics
  • DNA / metabolism
  • Endoderm / cytology
  • Endoderm / embryology
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox
  • Lung / embryology*
  • Mice
  • Organ Specificity
  • Organogenesis
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics


  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Foxp2 protein, mouse
  • Foxp4 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • DNA