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 journalArticle

6 Citations (Scopus)

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

Fingerprint

Mesoderm
Lung
Surface-Active Agents
Embryonic Structures
Saccule and Utricle
Alveolar Epithelial Cells
Apnea
Premature Infants
Cause of Death
Proteins
Transcription Factors
Epithelium
Gases
Parturition
Genes

Keywords

  • Fgf10
  • Lung development
  • Mesenchyme
  • Pbx1

ASJC Scopus subject areas

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

Cite this

Li, W., Lin, C. Y., Shang, C., Han, P., Xiong, Y., Lin, C. J., ... 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

Pbx1 activates Fgf10 in the mesenchyme of developing lungs. / Li, Wei; Lin, Chieh Yu; Shang, Ching; Han, Pei; Xiong, Yiqin; Lin, Chien Jung; Yang, Jing; Selleri, Licia; Chang, Ching-Pin.

In: Genesis, Vol. 52, No. 5, 2014, p. 399-407.

Research output: Contribution to journalArticle

Li, W, Lin, CY, Shang, C, Han, P, Xiong, Y, Lin, CJ, Yang, J, Selleri, L & Chang, C-P 2014, 'Pbx1 activates Fgf10 in the mesenchyme of developing lungs', Genesis, vol. 52, no. 5, pp. 399-407. https://doi.org/10.1002/dvg.22764
Li W, Lin CY, Shang C, Han P, Xiong Y, Lin CJ et al. Pbx1 activates Fgf10 in the mesenchyme of developing lungs. Genesis. 2014;52(5):399-407. https://doi.org/10.1002/dvg.22764
Li, Wei ; Lin, Chieh Yu ; Shang, Ching ; Han, Pei ; Xiong, Yiqin ; Lin, Chien Jung ; Yang, Jing ; Selleri, Licia ; Chang, Ching-Pin. / Pbx1 activates Fgf10 in the mesenchyme of developing lungs. In: Genesis. 2014 ; Vol. 52, No. 5. pp. 399-407.
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