Beta1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion.
BACKGROUND
There is a major discrepancy between the in vitro and in vivo results regarding the role of beta1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of beta1 integrins suggested that epidermis can form and be maintained in their absence, while in vitro data have shown a fundamental role for these adhesion receptors in stem/progenitor cell expansion and differentiation.


RESULTS
To elucidate this discrepancy we generated hypomorphic mice expressing reduced beta1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with beta1-deficient keratinocytes. Surprisingly we found that upon aging these abnormalities attenuated due to a rapid expansion of cells, which escaped or compensated for the down-regulation of beta1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the beta1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of beta1 integrin expressing keratinocytes was even further accelerated in situations of increased keratinocyte proliferation such as wound healing.


CONCLUSIONS
These data demonstrate that expression of beta1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis.
Piwko-Czuchra
Aleksandra
A
Max Planck Institute of Biochemistry, Department of Molecular Medicine, Martinsried, Germany.
Koegel
Heidi
H
Meyer
Hannelore
H
Bauer
Martina
M
Werner
Sabine
S
Brakebusch
Cord
C
Fässler
Reinhard
R
D000375:Aging / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002448:Cell Adhesion; D002452:Cell Count; D049109:Cell Proliferation; D018389:Codon, Nonsense / Q000235:genetics; D003433:Crosses, Genetic; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D019426:Integrases / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D053555:Keratin-5 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D010641:Phenotype; D011995:Recombination, Genetic / Q000235:genetics; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D018389:Codon, Nonsense; D019012:Integrin beta1; D053555:Keratin-5; C045073:Cre recombinase; D019426:Integrases