Pbx1 activates Fgf10 in the mesenchyme of developing lungs

Wei Li, Chieh Yu Lin, Ching Shang, Pei Han, Yiqin Xiong, Chien Jung Lin, Jing Yang, Licia Selleri, Ching Pin Chang

Research output: Contribution to journalLetter

6 Scopus citations

Abstract

Summary: Insufficiency of surfactants is a core factor in respiratory distress syndrome, which causes apnea and neonatal death, particularly in preterm infants. Surfactant proteins are secreted by alveolar type II cells in the lung epithelium, the differentiation of which is regulated by Fgf10 elaborated by the adjacent mesenchyme. However, the molecular regulation of mesenchymal Fgf10 during lung development has not been fully understood. Here, we show that Pbx1, a homeodomain transcription factor, is required in the lung mesenchyme for the expression of Fgf10. Mouse embryos lacking Pbx1 in the lung mesenchyme show compact terminal saccules and perinatal lethality with failure of postnatal alveolar expansion. Mutant embryos had severely reduced expression of Fgf10 and surfactant genes (Spa, Spb, Spc, and Spd) that are essential for alveolar expansion for gas exchange at birth. Molecularly, Pbx1 directly binds to the Fgf10 promoter and cooperates with Meis and Hox proteins to transcriptionally activate Fgf10. Our results thus show how Pbx1 controls Fgf10 in the developing lung. genesis 52:399-407, 2014.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalGenesis
Volume52
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Fgf10
  • Lung development
  • Mesenchyme
  • Pbx1

ASJC Scopus subject areas

  • Endocrinology
  • Cell Biology
  • Genetics
  • Medicine(all)

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  • Cite this

    Li, W., Lin, C. Y., Shang, C., Han, P., Xiong, Y., Lin, C. J., Yang, J., Selleri, L., & Chang, C. P. (2014). Pbx1 activates Fgf10 in the mesenchyme of developing lungs. Genesis, 52(5), 399-407. https://doi.org/10.1002/dvg.22764