GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo

Yuzhen Zhang, Nibedita Rath, Sridhar Hannenhalli, Zhishan Wang, Thomas Cappola, Shioko Kimura, Elena Atochina-Vasserman, Min Min Lu, Michael F. Beers, Edward E. Morrisey

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58 Citations (Scopus)

Abstract

In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary clysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf 1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalDevelopment
Volume134
Issue number1
DOIs
Publication statusPublished - Jan 2007
Externally publishedYes

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Keywords

  • GATA
  • Ling
  • Mouse
  • Nkx
  • Synergy
  • Transcription factor

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Zhang, Y., Rath, N., Hannenhalli, S., Wang, Z., Cappola, T., Kimura, S., ... Morrisey, E. E. (2007). GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo. Development, 134(1), 189-198. https://doi.org/10.1242/dev.02720