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Published online
doi:10.1083/jcb.200608125
The Journal of Cell Biology, Vol. 177, No. 3, 501-513
The Rockefeller University Press, 0021-9525 $30.00
© Lorenz et al.
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Article

Integrin-linked kinase is required for epidermal and hair follicle morphogenesis



Katrin Lorenz1, Carsten Grashoff1, Robert Torka1, Takao Sakai1, Lutz Langbein2, Wilhelm Bloch3, Monique Aumailley4, and Reinhard Fässler1

1 Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany
2 Division of Cell Biology, German Cancer Research Center, D-69120 Heidelberg, Germany
3 Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany
4 Department of Biochemistry, University of Cologne, 50923 Cologne, Germany

Correspondence to Reinhard Fässler: faessler{at}biochem.mpg.de

Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal–dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers.

The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.

K. Lorenz, C. Grashoff, and R. Torka contributed equally to this paper.

Abbreviations used in this paper: BM, basement membrane; DEJ, dermal–epidermal junction; DP, dermal papilla; FA, focal adhesion; FC, focal complex; GSK, glycogen synthase kinase; HF, hair follicle; HM, hair matrix; HS, hair shaft; ILK, integrin-linked kinase; IRS, inner root sheath; ORS, outer root sheath; P, postnatal day; PKB, protein kinase B; TA, transient amplifying.


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