Pbx1 activates Fgf10 in the mesenchyme of developing lungs. Issue 5 (14th March 2014)

• Record Type: Journal Article
• Authors: Li, Wei; Lin, Chieh‐Yu; Shang, Ching; Han, Pei; Xiong, Yiqin; Lin, Chien‐Jung; Yang, Jing; Selleri, Licia; Chang, Ching‐Pin
• Is Part Of: Genesis. Volume 52:Issue 5(2014:May)
• Page Start: 399
• Page End: 407
• Publication Date: 2014-03-14
• Subjects: Developmental genetics -- Periodicals; Genetics -- Periodicals; Developmental biology -- Periodicals; Embryology -- Periodicals; Genetic regulation -- Periodicals; 576.5
• DOI: 10.1002/dvg.22764
• Languages: English
• ISSNs: 1526-954X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>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 <italic>Fgf10</italic>. Mouse embryos lacking <italic>Pbx1</italic> in the lung mesenchyme show compact terminal saccules and perinatal lethality with failure of postnatal alveolar expansion. Mutant embryos had severely reduced expression of <italic>Fgf10</italic> and surfactant genes (<italic>Spa</italic>, <italic>Spb</italic>, <italic>Spc</italic>, and <italic>Spd</italic>) that are essential for alveolar expansion for gas exchange at birth. Molecularly, Pbx1 directly binds to the <italic>Fgf10</italic> promoter and cooperates with Meis and Hox proteins to transcriptionally activate <italic>Fgf10</italic>. Our results thus show how Pbx1 controls <italic>Fgf10</italic> in the developing lung. genesis 52:399–407, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>