P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis

Summary: During epithelial morphogenesis, in vivo, epithelial cells form cysts enclosing a single, hollow lumen and extend protrusions as a precursor for tubulogenesis. Cell-cell adhesions (e.g., cadherins) contribute to successful execution of these processes; while there are many different cadheri...

Full description

Saved in:
Bibliographic Details
Main Authors: Sydnie K. Tran, Jessanne Y. Lichtenberg, Corinne E. Leonard, Jessica R. Williamson, Hazel R. Sterling, Grace K. Panek, Amanda H. Pearson, Santiago Lopez, Christopher A. Lemmon, Daniel E. Conway, Priscilla Y. Hwang
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422500104X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832557496363909120
author Sydnie K. Tran
Jessanne Y. Lichtenberg
Corinne E. Leonard
Jessica R. Williamson
Hazel R. Sterling
Grace K. Panek
Amanda H. Pearson
Santiago Lopez
Christopher A. Lemmon
Daniel E. Conway
Priscilla Y. Hwang
author_facet Sydnie K. Tran
Jessanne Y. Lichtenberg
Corinne E. Leonard
Jessica R. Williamson
Hazel R. Sterling
Grace K. Panek
Amanda H. Pearson
Santiago Lopez
Christopher A. Lemmon
Daniel E. Conway
Priscilla Y. Hwang
author_sort Sydnie K. Tran
collection DOAJ
description Summary: During epithelial morphogenesis, in vivo, epithelial cells form cysts enclosing a single, hollow lumen and extend protrusions as a precursor for tubulogenesis. Cell-cell adhesions (e.g., cadherins) contribute to successful execution of these processes; while there are many different cadherins, one less studied cadherin in epithelial morphogenesis is P-cadherin (CDH3). Here, we investigated the role of CDH3 on successful lumen formation and cell protrusions, using three-dimensional cultures of Madin-Darby canine kidney (MDCK) and CDH3 knockout cell lines. We show that depletion of CDH3 leads to perturbations of hollow lumen formation associated with defects in cell protrusions and tubulogenesis, mediated by Rho/ROCK pathway. CDH3 knockout cells exert lower forces on the surrounding environment compared to wild-type cells, suggesting CDH3 acts as a mechanosensor for stable cell protrusion establishment. Together, our data suggest that CDH3 has an essential function during epithelial morphogenesis by contributing to lumen formation and cell protrusions.
format Article
id doaj-art-224b8e03a04942118a1e5aff44724a26
institution Kabale University
issn 2589-0042
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-224b8e03a04942118a1e5aff44724a262025-02-03T04:16:50ZengElsevieriScience2589-00422025-02-01282111844P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesisSydnie K. Tran0Jessanne Y. Lichtenberg1Corinne E. Leonard2Jessica R. Williamson3Hazel R. Sterling4Grace K. Panek5Amanda H. Pearson6Santiago Lopez7Christopher A. Lemmon8Daniel E. Conway9Priscilla Y. Hwang10Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Mechanical Engineering, Iowa State University, Ames, IA 50011, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, Rice University, Houston, TX 77251, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USADepartment of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USA; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA; Corresponding authorSummary: During epithelial morphogenesis, in vivo, epithelial cells form cysts enclosing a single, hollow lumen and extend protrusions as a precursor for tubulogenesis. Cell-cell adhesions (e.g., cadherins) contribute to successful execution of these processes; while there are many different cadherins, one less studied cadherin in epithelial morphogenesis is P-cadherin (CDH3). Here, we investigated the role of CDH3 on successful lumen formation and cell protrusions, using three-dimensional cultures of Madin-Darby canine kidney (MDCK) and CDH3 knockout cell lines. We show that depletion of CDH3 leads to perturbations of hollow lumen formation associated with defects in cell protrusions and tubulogenesis, mediated by Rho/ROCK pathway. CDH3 knockout cells exert lower forces on the surrounding environment compared to wild-type cells, suggesting CDH3 acts as a mechanosensor for stable cell protrusion establishment. Together, our data suggest that CDH3 has an essential function during epithelial morphogenesis by contributing to lumen formation and cell protrusions.http://www.sciencedirect.com/science/article/pii/S258900422500104XCell biologyFunctional aspects of cell biology
spellingShingle Sydnie K. Tran
Jessanne Y. Lichtenberg
Corinne E. Leonard
Jessica R. Williamson
Hazel R. Sterling
Grace K. Panek
Amanda H. Pearson
Santiago Lopez
Christopher A. Lemmon
Daniel E. Conway
Priscilla Y. Hwang
P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
iScience
Cell biology
Functional aspects of cell biology
title P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
title_full P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
title_fullStr P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
title_full_unstemmed P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
title_short P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis
title_sort p cadherin dependent adhesions are required for single lumen formation and hgf mediated cell protrusions during epithelial morphogenesis
topic Cell biology
Functional aspects of cell biology
url http://www.sciencedirect.com/science/article/pii/S258900422500104X
work_keys_str_mv AT sydniektran pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT jessanneylichtenberg pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT corinneeleonard pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT jessicarwilliamson pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT hazelrsterling pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT gracekpanek pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT amandahpearson pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT santiagolopez pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT christopheralemmon pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT danieleconway pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis
AT priscillayhwang pcadherindependentadhesionsarerequiredforsinglelumenformationandhgfmediatedcellprotrusionsduringepithelialmorphogenesis