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
Open Access
- 15 October 2005
- journal article
- Published by The Company of Biologists in Development
- Vol. 132 (20), 4533-4544
- https://doi.org/10.1242/dev.02019
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- ATP-dependent nucleosome remodelling: factors and functionsJournal of Cell Science, 2004
- Covering the limb – formation of the integumentJournal of Anatomy, 2003
- Epithelial barrier function: assembly and structural features of the cornified cell envelopeBioEssays, 2002
- Functions of FGF signalling from the apical ectodermal ridge in limb developmentNature, 2002
- Claudin-based tight junctions are crucial for the mammalian epidermal barrierThe Journal of cell biology, 2002
- Epidermal Stem Cells as Targets for Gene TransferHuman Gene Therapy, 2000
- Lipids and barrier function of the skinActa Dermato-Venereologica, 2000
- Expression Cloning of Human Corneodesmosin Proves Its Identity with the Product of the S Gene and Allows Improved Characterization of Its Processing during Keratinocyte DifferentiationPublished by Elsevier BV ,1998
- The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins.The Journal of cell biology, 1993
- Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox geneNature, 1992