The Mouse Snail Gene Encodes a Key Regulator of the Epithelial-Mesenchymal Transition

The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 01/2002; 21(23):8184-8. DOI: 10.1128/MCB.21.23.8184-8188.2001
Source: PubMed


Snail family genes encode DNA binding zinc finger proteins that act as transcriptional repressors. Mouse embryos deficient
for the Snail (Sna) gene exhibit defects in the formation of the mesoderm germ layer. In Sna
−/− mutant embryos, a mesoderm layer forms and mesodermal marker genes are induced but the mutant mesoderm is morphologically
abnormal. Lacunae form within the mesoderm layer of the mutant embryos, and cells lining these lacunae retain epithelial characteristics.
These cells resemble a columnar epithelium and have apical-basal polarity, with microvilli along the apical surface and intercellular
electron-dense adhesive junctions that resemble adherens junctions. E-cadherin expression is retained in the mesoderm of the
−/− embryos. These defects are strikingly similar to the gastrulation defects observed insnail-deficient Drosophila embryos, suggesting that the mechanism of repression of E-cadherin transcription by Snail family proteins may have been present
in the metazoan ancestor of the arthropod and mammalian lineages.

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Available from: Rulang Jiang, Jan 06, 2015
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    • "Certain proteins relevant to phenotypic developmental changes in stem cells and transformed cells have been described (Zheng and Kang, 2014). The transcriptional repressor Snail is essential for gastrulation and mesoderm formation during mammalian development (Carver et al., 2001). Snail levels increase in transformed cells. "
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    ABSTRACT: Reversion of the malignant phenotype of erbB2-transformed cells can be driven by anti-erbB2/neu monoclonal antibodies (mAbs), which disrupt the receptor's kinase activity. We examined the biologic effects of IFN-γ alone or after anti-erbB2/neu mAb treatment of erbB2-positive cells. IFN-γ had no effect on its own. Treatment of the tumors with anti-erbB2/neu mAbs followed by IFN-γ led to dramatic inhibition of tumor growth in vitro and in vivo with minimal mAb dosing. Sequential therapy enhanced the effects of chemotherapy. Moreover, IFN-γ with mAb treatment of mice with IFNγR knockdown tumors did not demonstrate marked synergistic eradication effects, indicating an unexpected role of IFN-γ on the tumor itself. Additionally, mAb and IFN-γ treatment also induced immune host responses that enhanced tumor eradication. Biochemical analyses identified loss of Snail expression in tumor cells, reflecting diminution of tumor-stem-cell-like properties as a consequence of altered activity of GSK3-β and KLF molecules.
    Cell Reports 09/2015; 12(12). DOI:10.1016/j.celrep.2015.08.044 · 8.36 Impact Factor
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    • "Historically, the Snail family is most well known for roles in embryonic development [14] however, Snail proteins have also been shown to play a prominent role in hematopoiesis [15]. Due to embryonic lethality resulting from germline deletion of Snai1, the hematopoietic functions of this family member have not yet been defined [16] [17]. The germline deletion of Snai2 (g2KO) is viable with piebaldism of variable penetrance [18]. "
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    ABSTRACT: Transcriptional regulation of gene expression is a key component of orchestrating proper immune cell development and function. One strategy for maintaining these transcriptional programs has been the evolution of transcription factor families with members possessing overlapping functions. Using the germ line deletion of Snai2 combined with the hematopoietic specific deletion of Snai3, we report that these factors function redundantly to preserve the development of B and T cells. Such animals display severe lymphopenia, alopecia and dermatitis as well as profound autoimmunity manifested by the production of high levels of autoantibodies as early as 3weeks of age and die by 30days after birth. Autoantibodies included both IgM and IgG isotypes and were reactive against cytoplasmic and membranous components. A regulatory T cell defect contributed to the autoimmune response in that adoptive transfer of wild type regulatory T cells alleviated symptoms of autoimmunity. Additionally, transplantation of Snai2/Snai3 double deficient bone marrow into Snai2 sufficient Rag2(-/-) recipients resulted in autoantibody generation. The results demonstrated that appropriate expression of Snai2 and Snai3 in cells of hematopoietic derivation plays an important role in development and maintenance of immune tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cellular Immunology 02/2015; 295(1):1-18. DOI:10.1016/j.cellimm.2015.02.009 · 1.92 Impact Factor
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    • "Interestingly, Slug knockout mice are viable with no major phenotype (Jiang et al., 1998), although loss of the closely related gene Snail causes early embryonic lethality due to problems with gastrulation (Carver et al., 2001). It is therefore possible that Snail compensates for the loss of Slug during early development, masking a potential role for Slug in this process. "
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    ABSTRACT: The contribution of epithelial-to-mesenchymal transitions (EMT) in both developmental and pathological conditions has been widely recognized and studied. In a parallel process, governed by a similar set of signaling and transcription factors, endothelial-to-mesenchymal transitions (EndoMT) contribute to heart valve formation and the generation of cancer-associated fibroblasts. During angiogenic sprouting, endothelial cells express many of the same genes and break down basement membrane; however, they retain intercellular junctions and migrate as a connected train of cells rather than as individual cells. This has been termed a partial endothelial-to-mesenchymal transition. A key regulatory check-point determines whether cells undergo a full or a partial epithelial-to-mesenchymal transitions/endothelial-to-mesenchymal transition; however, very little is known about how this switch is controlled. Here we discuss these developmental/pathological pathways, with a particular focus on their role in vascular biology. © 2014 American Heart Association, Inc.
    Arteriosclerosis Thrombosis and Vascular Biology 11/2014; 35(2). DOI:10.1161/ATVBAHA.114.303220 · 6.00 Impact Factor
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