TTF-1 regulates lung epithelial morphogenesis

Dev Biol. 1995 Dec;172(2):694-8. doi: 10.1006/dbio.1995.8080.

Abstract

TTF-1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. In vitro, TTF-1 can activate the promoter of thyroid- and pulmonary-specific genes. We postulated that TTF-1 not only is essential for the activation of tissue-specific genes, but also may directly participate in epithelial cell morphogenesis. To test this postulate, we used an antisense oligonucleotide inhibitory strategy in an in vitro model of embryonic mouse lung branching morphogenesis. This strategy suppressed TTF-1 translation and inhibited lung branching morphogenesis. The resulting abnormal phenotype was characterized by hyperplastic and unorganized proliferation of epithelial cells in the airways. The mesenchymal compartment of the lung appeared to be unaffected. These results demonstrate, for the first time, that the expression of a homeoprotein transcriptional regulator is necessary for lung epithelial morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division
  • Cells, Cultured
  • Epithelium / embryology
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / physiology
  • Lung / embryology*
  • Mice
  • Molecular Sequence Data
  • Morphogenesis
  • Nuclear Proteins / physiology*
  • Thyroid Nuclear Factor 1
  • Transcription Factors / physiology*

Substances

  • Homeodomain Proteins
  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors

Associated data

  • GENBANK/U33749