title: Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification.
abstract: 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.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS/UMII, Montpellier, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zanet
authors.forename: Sophie
authors.initials: S
authors.lastname: Pibre
authors.forename: Chantal
authors.initials: C
authors.lastname: Jacquet
authors.forename: Angel
authors.initials: A
authors.lastname: Ramirez
authors.forename: Ignacio Moreno
authors.initials: IM
authors.lastname: de Alborán
authors.forename: Alberto
authors.initials: A
authors.lastname: Gandarillas
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D049108:Cell Enlargement; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D004817:Epidermis / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D018859:Hair Follicle / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011003:Ploidies; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D014945:Wound Healing / Q000502:physiology
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc