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First published online September 28, 2005
doi: 10.1242/10.1242/dev.02019


Development 132, 4533-4544 (2005)
Published by The Company of Biologists 2005


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Temporally controlled targeted somatic mutagenesis in embryonic surface ectoderm and fetal epidermal keratinocytes unveils two distinct developmental functions of BRG1 in limb morphogenesis and skin barrier formation

Arup Kumar Indra1,2, Valérie Dupé1, Jean-Marc Bornert1, Nadia Messaddeq1, Moshe Yaniv4, Manuel Mark1,2, Pierre Chambon2,3,* and Daniel Metzger1,2,*

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, BP 10142-67404, Illkirch, C.U. de Strasbourg, France
2 Institut Clinique de la Souris (ICS), BP 10142, CU de Strasbourg, 67404 Illkirch, France
3 Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France
4 Unité Expression Génétique et Maladies, CNRS URA 1644, Département de Biologie du Développement, Institut Pasteur, 75724 Paris, France

* Authors for correspondence (e-mail: metzger{at}igbmc.u-strasbg.fr and chambon{at}igbmc.u-strasbg.fr)

Accepted 1 August 2005

Animal SWI2/SNF2 protein complexes containing either the brahma (BRM) or brahma-related gene 1 (BRG1) ATPase are involved in nucleosome remodelling and may control the accessibility of sequence-specific transcription factors to DNA. In vitro studies have indicated that BRM and BRG1 could regulate the expression of distinct sets of genes. However, as mice lacking BRM are viable and fertile, BRG1 might efficiently compensate for BRM loss. By contrast, as Brg1-null fibroblasts are viable but Brg1-null embryos die during the peri-implantation stage, BRG1 might exert cell-specific functions. To further investigate the in vivo role of BRG1, we selectively ablated Brg1 in keratinocytes of the forming mouse epidermis. We show that BRG1 is selectively required for epithelial-mesenchymal interactions in limb patterning, and during keratinocyte terminal differentiation, in which BRM can partially substitute for BRG1. By contrast, neither BRM nor BRG1 are essential for the proliferation and early differentiation of keratinocytes, which may require other ATP-dependent nucleosome-remodelling complexes. Finally, we demonstrate that cell-specific targeted somatic mutations can be created at various times during the development of mouse embryos cell-specifically expressing the tamoxifen-activatable Cre-ERT2 recombinase.

Key words: Targeted somatic mutagenesis, Cre-Lox, Epidermis, Limb, SNF2ß-BRG1


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