NDLI: Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

Content Provider	PubMed Central
Author	Yates, Laura L. Carsten, Schnatwinkel Hazelwood, Lee Lauren, Chessum Paudyal, Anju Hilton, Helen Romero, M. Rosario Wilde, Jonathan Bogani, Debora Sanderson, Jeremy Caroline, Formstone Murdoch, Jennifer N. Niswander, Lee A. Greenfield, Andy Dean, Charlotte H.
Copyright Year	2012
Abstract	During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in Scrib Crc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen morphogenesis by maintaining cell–cell contacts. Thus we reveal novel and important roles for Scrib in lung development operating via the PCP pathway, and in regulating junctional complexes and cell cohesion.
Related Links	http://dx.doi.org/10.1016/j.ydbio.2012.11.012
Starting Page	267
File Format	PDF
ISSN	1095564X
e-ISSN	1095564X
Journal	Developmental Biology
Issue Number	2
Volume Number	373
Language	English
Publisher	Elsevier
Publisher Date	2013-01-15
Access Restriction	Open
Rights Holder	Elsevier
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization

Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

Epithelial relaxation mediated by the myosin phosphatase regulator Mypt1 is required for brain ventricle lumen expansion and hindbrain morphogenesis

Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors

Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid

Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis

Foxg1 Is Required for Morphogenesis and Histogenesis of the Mammalian Inner Ear

A fat body-derived apical extracellular matrix enzyme is transported to the tracheal lumen and is required for tube morphogenesis in Drosophila

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

Similar Documents

Epithelial β1 integrin is required for lung branching morphogenesis and alveolarization

Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

Epithelial relaxation mediated by the myosin phosphatase regulator Mypt1 is required for brain ventricle lumen expansion and hindbrain morphogenesis

Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors

Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid

Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis

Foxg1 Is Required for Morphogenesis and Histogenesis of the Mammalian Inner Ear

A fat body-derived apical extracellular matrix enzyme is transported to the tracheal lumen and is required for tube morphogenesis in Drosophila

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung