title: Pbx1 activates Fgf10 in the mesenchyme of developing lungs.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Ching
authors.initials: C
authors.lastname: Shang
authors.forename: Pei
authors.initials: P
authors.lastname: Han
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Xiong
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Licia
authors.initials: L
authors.lastname: Selleri
authors.forename: Ching-Pin
authors.initials: CP
authors.lastname: Chang
mesh_terms: D000818:Animals; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000254:growth & development* / Q000378:metabolism; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D018398:Homeodomain Proteins; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors
keywords: Fgf10; Pbx1; lung development; mesenchyme