Different consequences of beta1 integrin deletion in neonatal and adult mouse epidermis reveal a context-dependent role of integrins in regulating proliferation, differentiation, and intercellular communication.
There are conflicting reports of the consequences of deleting beta1 integrins from the epidermis of transgenic mice. Epidermal thinning with normal differentiation and lack of inflammation has been observed; conversely, epidermal thickening, abnormal differentiation, and dermal fibrosis can occur. beta1 integrin deletion results in decreased epidermal proliferation, yet on wounding the proliferative defect is overcome. To distinguish primary from secondary consequences of beta1 integrin loss, we compared epidermal beta1 deletion at E14.5 via K5Cre and 4-hydroxy-tamoxifen induced deletion in adulthood via K14CreER. As reported previously, there was dermo-epidermal splitting, inflammation, reduced proliferation, and hair follicle and sebaceous gland loss in 30-d-old K5Cre beta1-null mice. These changes were not observed 30 d after beta1 integrin deletion in adult epidermis, however, and there were no changes in the hair follicle stem cell compartment. Deletion in adult epidermis revealed a previously unreported correlation between the level of beta1 integrins and proliferation in the interfollicular epidermis that was remarkably consistent with human epidermis. In addition, the number of melanocytes in interfollicular epidermis was greatly increased. Our results highlight the context-dependent effects of beta1 integrin deletion and suggest that inflammation may be responsible for some of the K5Cre beta1-null phenotype.
López-Rovira
Teresa
T
Keratinocyte Laboratory, Cancer Research UK London Research Institute, London, UK.
Silva-Vargas
Violeta
V
Watt
Fiona M
FM
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D004817:Epidermis / Q000254:growth & development / Q000502:physiology*; D017353:Gene Deletion; D019012:Integrin beta1 / Q000235:genetics*; D016023:Integrins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015595:Skin Aging; D012879:Skin Physiological Phenomena
D019012:Integrin beta1; D016023:Integrins