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Molecular and Cellular Biology, September 2006, p. 6957-6970, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00075-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rac1 Is Crucial for Hair Follicle Integrity but Is Not Essential for Maintenance of the Epidermis{dagger}

Anna Chrostek,1 Xunwei Wu,1,{ddagger} Fabio Quondamatteo,2 Rong Hu,1 Anna Sanecka,1 Catherin Niemann,3 Lutz Langbein,4 Ingo Haase,5 and Cord Brakebusch1*

Heisenberg Group "Regulation of Cytoskeletal Organization," Max Planck Institute of Biochemistry, Martinsried, Germany,1 Department of Histology, Georg August University of Göttingen, Göttingen, Germany,2 Institute of Pathology, Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany,3 Department of Cell Biology, German Cancer Research Center, Heidelberg, Germany,4 Department of Dermatology, Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany5

Received 12 January 2006/ Returned for modification 4 February 2006/ Accepted 3 July 2006

Rac1 is a small GTPase that regulates the actin cytoskeleton but also other cellular processes. To investigate the function of Rac1 in skin, we generated mice with a keratinocyte-restricted deletion of the rac1 gene. Rac1-deficient mice lost nearly all of their hair within a few weeks after birth. The nonpermanent part of mutant hair follicles developed constrictions; lost expression of hair follicle-specific keratins, E-cadherin, and {alpha}6 integrin; and was eventually removed by macrophages. The permanent part of hair follicles and the sebaceous glands were maintained, but no regrowth of full-length hair follicles was observed. In the skin of mutant mice, epidermal keratinocytes showed normal differentiation, proliferation, cell-cell contacts, and basement membrane deposition, demonstrating no obvious defects of Rac1-deficient epidermis in vivo. In vitro, Rac1-null keratinocytes displayed a strong spreading defect and slightly impaired adhesion. These data show that Rac1 plays an important role in sustaining the integrity of the lower part of hair follicles but not in maintenance of the epidermis.

* Corresponding author. Phone: 0045-353-26043. Fax: 0045-353-26081. E-mail: cord{at}pai.ku.dk.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

§ Present address: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsreid, Germany.

{ddagger} Present address: Group of Developmental Biology, Institute of Molecular Pathology, Copenhagen University, 2100 Copenhagen, Denmark.

Molecular and Cellular Biology, September 2006, p. 6957-6970, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00075-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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