ArticlePLoS genetics2017
Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Single-cell multiomics analysis reveals CTCF as a key regulator of lung morphogenesis and progenitor maintenance.Nature communications · 2025Article
- Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis.Nature communications · 2025Article
- Genome-wide identification of potential odontogenic genes involved in the dental epithelium-mesenchymal interaction during early odontogenesis.BMC genomics · 2023Article
- Plasticity in airway smooth muscle differentiation during mouse lung development.Developmental cell · 2023Article
- Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls.Respiratory research · 2023Article
- Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis.International journal of molecular sciences · 2022Article
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time.International journal of molecular sciences · 2021Review
- RhoA/ROCK signaling pathway and astrocytes in ischemic stroke.Metabolic brain disease · 2021Review
- Implications for Extracellular Matrix Interactions With Human Lung Basal Stem Cells in Lung Development, Disease, and Airway Modeling.Frontiers in pharmacology · 2021Review
- Range of SHH signaling in adrenal gland is limited by membrane contact to cells with primary cilia.The Journal of cell biology · 2020Article
- Extracellular matrix dynamics in tubulogenesis.Cellular signalling · 2020Review
- Extracellular Matrix Remodeling During Palate Development.Organogenesis · 2020Review
- Fgf10/Fgfr2b Signaling Orchestrates the Symphony of Molecular, Cellular, and Physical Processes Required for Harmonious Airway Branching Morphogenesis.Frontiers in cell and developmental biology · 2020Review
- Smooth muscle differentiation shapes domain branches during mouse lung development.Development (Cambridge, England) · 2019Article
- Alteration of cystic airway mesenchyme in congenital pulmonary airway malformation.Scientific reports · 2019Article
- Review
- Multiple roles of epithelial heparan sulfate in stomach morphogenesis.Journal of cell science · 2018Article
- From top to bottom: Cell polarity in Hedgehog and Wnt trafficking.BMC biology · 2018Review
- Taking the Occam's Razor Approach to Hedgehog Lipidation and Its Role in Development.Journal of developmental biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The tree-like structure of the mammalian lung is generated from branching morphogenesis, a reiterative process that is precisely regulated by numerous factors. How the cell surface and extra cellular matrix (ECM) molecules regulate this process is still poorly understood. Herein, we show that epithelial deletion of Heparan Sulfate (HS) synthetase Ext1 resulted in expanded branching tips and reduced branching number, associated with several mesenchymal developmental defects. We further demonstrate an expanded Fgf10 expression and increased FGF signaling activity in Ext1 mutant lungs, suggesting a cell non-autonomous mechanism. Consistent with this, we observed reduced levels of SHH signaling which is responsible for suppressing Fgf10 expression. Moreover, reactivating SHH signaling in mutant lungs rescued the tip dilation phenotype and attenuated FGF signaling. Importantly, the reduced SHH signaling activity did not appear to be caused by decreased Shh expression or protein stability; instead, biologically active form of SHH proteins were reduced in both the Ext1 mutant epithelium and surrounding wild type mesenchymal cells. Together, our study highlights the epithelial HS as a key player for dictating SHH signaling critical for lung morphogenesis.
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Registered trials
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.