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| Subject Categories: Chromatin & Transcription | Development |
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| The EMBO Journal
(2002) 21, 3402–3413, doi: 10.1093/emboj/cdf331 |
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| Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled |
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| Benoit Chapellier1, Manuel Mark1, Nadia Messaddeq1, Cécile Calléja1, Xavier Warot1, Jacques Brocard1, Christelle Gérard1, Mei Li1, Daniel Metzger1, Norbert B. Ghyselinck1, 2 and Pierre Chambon1, 2 |
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1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France 2 N.B.Ghyselinck and P.Chambon contributed equally to this work To whom correspondence should be addressed Pierre Chambon, chambon@igbmc.u-strasbg.fr Received 18 March 2002; Revised 29 April 2002; Accepted 6 May 2002. |
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| Abstract |
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To investigate the roles of retinoic acid (RA) receptors (RARs) in the physiology of epidermis that does not express RAR , conditional spatio-temporally controlled somatic mutagenesis was used to selectively ablate RAR in keratinocytes of RAR -null mice. Keratinocyte proliferation was maintained in adult mouse epidermis lacking both RAR and RAR, as well as in RAR-null mice. All RAR-mediated signalling pathways are therefore dispensable in epidermis for homeostatic keratinocyte renewal. However, topical treatment of mouse skin with selective retinoids indicated that RXR/RAR heterodimers, in which RXR transcriptional activity was subordinated to that of its RAR partner, were required for retinoid-induced epidermal hyperplasia, whereas RXR homodimers and RXR/RAR heterodimers were not involved. RA-induced keratinocyte proliferation was studied in mutant mice in which RXR, RXR and RAR, RAR, or RXR and RAR genes were specifically disrupted in either basal or suprabasal keratinocytes. We demonstrate that the topical retinoid signal is transduced by RXR/RAR heterodimers in suprabasal keratinocytes, which, in turn, stimulate proliferation of basal keratinocytes via a paracrine signal that may be heparin-binding EGF-like growth factor. |
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| Keywords: conditional somatic mutagenesis, heparin-binding EGF-like growth factor, nuclear receptor, paracrine control, synthetic retinoids |
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