Constitutively active Akt induces ectodermal defects and impaired BMP signaling

Aberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1 (myrAkt) in transgenic mice. Contrary to mice overexpressing wilt type Akt1 (Aktwt), these myrAkt mice display, in a dose-dependent manner, altered development of ectodermally derived organs such as hair, teeth, nails and epidermal glands. To identify the possible molecular mechanisms underlying these alterations, gene profiling approaches were employed. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein (BMP)-dependent signaling pathway, which leads to alterations in adult epidermal stem cells. Collectively, we show that epithelial tissue development and homeostasis is dependent on proper regulation of Akt expression and activity. Keywords: ectodermal development, Akt1, skin, transgenic mice Two (transgenic mice L60, L84 and LA) or three pools (control mice LC) from RNA whole skin extracts of same genotype were done and analyzed, individually, in mouse microarrays. Comparison was performed between the 4 different genotypes.