ArticleProceedings of the National Academy of Sciences of the United States of America2013
Lung epithelial branching program antagonizes alveolar differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 191 citations in OpenAlex.
- Svep1 orchestrates distal airway patterning and alveolar differentiation in murine lung development.eLife · 2026Article
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- BRD4 promotes endodermal cell fate during mammalian lung development.JCI insight · 2026Article
- LIN28-mediated gene regulatory loops synchronize transitions throughout organogenesis.Biochemistry and biophysics reports · 2025Article
- Review
- Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis.Nature communications · 2025Article
- HOXA5-driven transcriptional program in lung development.Developmental biology · 2025Article
- Morphogenic, molecular and cellular adaptations for unidirectional airflow in the chicken lung.Development (Cambridge, England) · 2025Article
- Morphogenesis and regeneration share a conserved core transition cell state program that controls lung epithelial cell fate.Developmental cell · 2025Article
- PRDM3/16 regulate chromatin accessibility required for NKX2-1 mediated alveolar epithelial differentiation and function.Nature communications · 2024Article
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- Sox9 is associated with two distinct patterning events during snake lung morphogenesis.Developmental biology · 2024Article
- The evolution ofEuropean respiratory review : an official journal of the European Respiratory Society · 2024Review
- Role of Sox9 in BPD and its effects on the Wnt/β-catenin pathway and AEC-II differentiation.Cell death discovery · 2024Article
- Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease.NPJ Regenerative medicine · 2024Article
- Inducible tricolor reporter mouse for parallel imaging of lysosomes, mitochondria, and microtubules.The Journal of cell biology · 2024Article
- PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiation and Function.bioRxiv : the preprint server for biology · 2023Article
- Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung.NPJ Regenerative medicine · 2023Article
- Hepatocyte-specific Sox9 knockout ameliorates acute liver injury by suppressing SHP signaling and improving mitochondrial function.Cell & bioscience · 2023Article
64 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 2 countries.
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Abstract
Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. Much progress has been made to understand each of the two processes individually; however, it is not clear whether the two processes are coordinated and how they are deployed at the correct time and location. Here we show that an epithelial branching morphogenesis program antagonizes alveolar differentiation in the mouse lung. We find a negative correlation between branching morphogenesis and alveolar differentiation temporally, spatially, and evolutionarily. Gain-of-function experiments show that hyperactive small GTPase Kras expands the branching program and also suppresses molecular and cellular differentiation of alveolar cells. Loss-of-function experiments show that SRY-box containing gene 9 (Sox9) functions downstream of Fibroblast growth factor (Fgf)/Kras to promote branching and also suppresses premature initiation of alveolar differentiation. We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9. The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.