Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print January 30, 2008
Mol. Biol. Cell 10.1091/mbc.E07-06-0526

A more recent version of this article appeared on April 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-06-0526v1
19/4/1462    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakrieko, K.-A.
Right arrow Articles by Dagnino, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakrieko, K.-A.
Right arrow Articles by Dagnino, L.

Submitted on June 4, 2007
Revised on January 9, 2008
Accepted on January 17, 2008

Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis

Kerry-Ann Nakrieko,* Ian Welch,{dagger} Holly Dupuis,* Dawn Bryce,* Agnieszka Pajak,* René St. Arnaud,{ddagger} Shoukat Dedhar,{sect} Sudhir J. A. D’Souza,* and Lina Dagnino*||

*Department of Physiology and Pharmacology, and Regulatory Biology and Functional Genomics Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario, Canada; {dagger}Animal Care and Veterinary Services, University of Western Ontario, London, Ontario, Canada; {ddagger}Shriners Hospital and McGill University, Montreal, Quebec, Canada; {sect}Department of Biochemistry and BC Cancer Agency, University of British Columbia, Vancouver, Canada, and ||Department of Paediatrics, Child Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada

Monitoring Editor: Asma Nusrat

Integrin-linked kinase (ILK) is key for cell survival, migration and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently, and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scratched keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

Address correspondence to: Sudhir J. A. D’Souza (sjdsouza{at}uwo.ca) or Lina Dagnino (ldagnino{at}uwo.ca)




This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
E. Ho, T. Irvine, G. J.A. Vilk, G. Lajoie, K. S. Ravichandran, S. J.A. D'Souza, and L. Dagnino
Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity
Mol. Biol. Cell, July 1, 2009; 20(13): 3033 - 3043.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
P. C. McDonald, A. B. Fielding, and S. Dedhar
Integrin-linked kinase - essential roles in physiology and cancer biology
J. Cell Sci., October 1, 2008; 121(19): 3121 - 3132.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.