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First published online 29 March 2005
doi: 10.1242/jcs.02298

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Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification

Jennifer Zanet^1,*, Sophie Pibre^1,*, Chantal Jacquet¹, Angel Ramirez², Ignacio Moreno de Alborán³ and Alberto Gandarillas^1,*,

¹ Institut de Génétique Moléculaire de Montpellier, CNRS/UMII, Montpellier, France
² Epithelial Damage, Repair and Tissue Engineering Program, CIEMAT, Madrid, Spain
³ Centro Nacional de Biotecnologia, CSIC, Madrid, Spain

Author for correspondence (e-mail: gandarillas{at}montp.inserm.fr)

Accepted 1 February 2005

The transcription factor Myc (c-Myc) plays an important role in cell growth and cell death, yet its physiological function remains unclear. Ectopic activation of Myc has been recently suggested to regulate cell mass, and Drosophila dmyc controls cellular growth and size independently of cell division. By contrast, it has been proposed that in mammals Myc controls cell division and cell number. To gain insights into this debate we have specifically knocked out Myc in epidermis. Myc epidermal knockout mice are viable and their keratinocytes continue to cycle, but they display severe skin defects. The skin is tight and fragile, tears off in areas of mechanical friction and displays impaired wound healing. Steady-state epidermis is thinner, with loss of the proliferative compartment and premature differentiation. Remarkably, keratinocyte cell size, growth and endoreplication are reduced, and stem cell amplification is compromised. The results provide new and direct evidence for a role for endogenous Myc in cellular growth that is required for hyperproliferative cycles and tissue homeostasis.

Key words: Cellular growth, Proliferation, Endoreduplication, Cell renewal, Polyploidy

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