QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 1, 137-149, January 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E07-08-0764v1 19/1/137    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Segrelles, C. Articles by Paramio, J. M. Search for Related Content PubMed PubMed Citation Articles by Segrelles, C. Articles by Paramio, J. M.

Constitutively Active Akt Induces Ectodermal Defects and Impaired Bone Morphogenetic Protein Signaling

Carmen Segrelles^*,, Marta Moral^*,, Corina Lorz^*,, Mirentxu Santos^*, Jerry Lu, José Luis Cascallana, M. Fernanda Lara^*, Steve Carbajal, Ana Belén Martínez-Cruz^*, Ramón García-Escudero^*, Linda Beltran, José C. Segovia^||, Ana Bravo, John DiGiovanni, and Jesús M. Paramio^*

*Molecular Oncology Unit, Division of Biomedicine, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, E-28040 Madrid, Spain; Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957; Department of Veterinary Clinical Sciences, Veterinary Pathology Unit, Veterinary Faculty, University of Santiago de Compostela, E-27002 Lugo, Spain; and ^||Flow Cytometry Unit, Division of Hematopoiesis, CIEMAT, E-28040 Madrid, Spain

Submitted August 7, 2007; Revised September 21, 2007; Accepted October 17, 2007
Monitoring Editor: M. Bishr Omary

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 noncell 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 wild-type Akt1 (Akt^wt), 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 used. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein-dependent signaling pathway. In addition, these mice also display 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.

These authors contributed equally to this work.

Address correspondence to: John DiGiovanni (jdigiovanni{at}mdanderson.org) or Jesús M. Paramio (jesusm.paramio{at}ciemat.es)

Abbreviations used: BMP, bone morphogenetic protein; HF, hair follicle.