Sox2 and Isl1 cooperate to orchestrate Merkel cell differentiation.

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Sox2 and Isl1 cooperate to orchestrate Merkel cell differentiation. Sox2 and Isl1 cooperate to orchestrate Merkel cell differentiation. (A) IF analysis of WT, Isl1cKO, Sox2cKO and Isl1 Sox2 2cKO mice, showing a further reduction in the number of K8+ (Krt8+) cells present in the 2cKO epidermis. (B) WMIF analysis confirmation of the cooperative effect of Sox2 and Isl1. Quantification of the number of K8+ cells per mm of epidermis is provided in C (WT versus Isl1cKO, P=0.8902; WT versus Sox2cKO, P<0.0001; Sox2cKO versus Isl1 Sox2 2cKO, P<0.0001). (D-F) Abrogation of Isl1 and Sox2 in mice results in dramatic loss of Atoh1-GFP+ cells in the back skin. (D) IF analysis of WT, Isl1cKO, Sox2cKO and Isl1 Sox2 2cKO mice showing a further reduction in the number of Atoh1GFP+ K8+ cells present in the 2cKO epidermis. (E) WMIF analysis confirms the cooperative effect of Sox2 and Isl1 in specifying Atoh1-GFP+ cells. (F) Quantification of Atoh1-GFP+ cells per mm of epidermis (WT versus Isl1cKO, P=0.4579; WT versus Sox2cKO, P<0.0001; Sox2cKO versus Isl1 Sox2 2cKO, P<0.0001). (G) WT, Isl1cKO, Sox2cKO and Isl1 Sox2 2cKO epidermis showed no differences in apoptosis, as measured by IF against activated caspase3. (H) Isl1 co-immunoprecipitates with Sox2 when expressed in 293T cells in vitro. Scale bars: 25 µm. Carolina N. Perdigoto et al. Development 2014;141:4690-4696 © 2014. Published by The Company of Biologists Ltd