| A perfusion-independent role of blood vessels in determining branching stereotypy of lung airways. | |
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MedLine Citation:
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PMID: 21558382 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Blood vessels have been shown to play perfusion-independent roles in organogenesis. Here, we examined whether blood vessels determine branching stereotypy of the mouse lung airways in which coordinated branching of epithelial and vascular tubes culminates in their co-alignment. Using different ablative strategies to eliminate the lung vasculature, both in vivo and in lung explants, we show that proximity to the vasculature is indeed essential for patterning airway branching. Remarkably, although epithelial branching per se proceeded at a nearly normal rate, branching stereotypy was dramatically perturbed following vascular ablation. Specifically, branching events requiring a rotation to change the branching plane were selectively affected. This was evidenced by either the complete absence or the shallow angle of their projections, with both events contributing to an overall flat lung morphology. Vascular ablation also led to a high frequency of ectopic branching. Regain of vascularization fully rescued arrested airway branching and restored normal lung size and its three-dimensional architecture. This role of the vasculature is independent of perfusion, flow or blood-borne substances. Inhibition of normal branching resulting from vascular loss could be explained in part by perturbing the unique spatial expression pattern of the key branching mediator FGF10 and by misregulated expression of the branching regulators Shh and sprouty2. Together, these findings uncovered a novel role of the vasculature in organogenesis, namely, determining stereotypy of epithelial branching morphogenesis. |
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Authors:
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Alon Lazarus; Pierre Marie Del-Moral; Ohad Ilovich; Eyal Mishani; David Warburton; Eli Keshet |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 138 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-11 Completed Date: 2011-07-21 Revised Date: 2012-05-10 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 2359-68 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, Hebrew University-Hadassah Medical School, and Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Communication Endothelial Cells / physiology Fibroblast Growth Factor 10 / biosynthesis Gene Expression Regulation, Developmental Hedgehog Proteins / biosynthesis In Situ Hybridization Lung / blood supply*, embryology* Membrane Proteins / biosynthesis Mice Mice, Inbred ICR Mice, Transgenic Morphogenesis Neovascularization, Physiologic Organ Culture Techniques Organogenesis* Polymerase Chain Reaction Vascular Endothelial Growth Factor A / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM096195/GM/NIGMS NIH HHS; R01 GM096195-02/GM/NIGMS NIH HHS; R01 HL075773/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fgf10 protein, mouse; 0/Fibroblast Growth Factor 10; 0/Hedgehog Proteins; 0/Membrane Proteins; 0/Shh protein, mouse; 0/Spry2 protein, mouse; 0/Vascular Endothelial Growth Factor A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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