Rac1 is crucial for hair follicle integrity but is not essential for maintenance of the epidermis.
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 alpha6 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.
Chrostek
Anna
A
Heisenberg Group-Regulation of Cytoskeletal Organization, Max Planck Institute of Biochemistry, Martinsried, Germany.
Wu
Xunwei
X
Quondamatteo
Fabio
F
Hu
Rong
R
Sanecka
Anna
A
Niemann
Catherin
C
Langbein
Lutz
L
Haase
Ingo
I
Brakebusch
Cord
C
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D017353:Gene Deletion; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000172:deficiency / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D013629:Tamoxifen; C016601:afimoxifene; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins