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Gene Review

Snai1  -  snail family zinc finger 1

Mus musculus

Synonyms: AI194338, Protein sna, Protein snail homolog 1, Sna, Sna1, ...
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Disease relevance of Snai1


Psychiatry related information on Snai1


High impact information on Snai1

  • The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression [3].
  • Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization [3].
  • Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals [3].
  • The Snail superfamily of zinc-finger transcription factors is involved in processes that imply pronounced cell movements, both during embryonic development and in the acquisition of invasive and migratory properties during tumour progression [9].
  • Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene [10].

Biological context of Snai1

  • To overcome this restriction, we generated a Snai1 conditional null allele by flanking the promoter and first two exons of the Snai1 gene with loxP sites [1].
  • Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties [10].
  • The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development [10].
  • The members of the Snail family of zinc-finger transcription factors have been implicated in the formation of distinct tissues within the developing vertebrate and invertebrate embryo [11].
  • We have isolated the mouse homologue of the Slu gene enabling us to analyse and compare the amino acid sequences and the patterns of expression of both Sna and Slu in the chick and mouse [11].

Anatomical context of Snai1

  • Snail/Snai1 is rapidly induced by Gli1 in vitro, and is coexpressed with Gli1 in human hair follicles and skin tumors [12].
  • We have recently generated a conditional allele of the Snai1 gene and examined its function during the formation of the neural crest and establishment of the left-right axis [13].
  • Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost [10].
  • In Sna(-/-) mutant embryos, a mesoderm layer forms and mesodermal marker genes are induced but the mutant mesoderm is morphologically abnormal [14].
  • We have detected features in the sequences that allow the unequivocal ascription of any family member to the Sna or Slu subfamilies and we have observed that, during early stages of development, many of the sites of Slu and Sna expression in the mouse and chick embryo are swapped [11].

Associations of Snai1 with chemical compounds

  • Snail's lysine residues 98 and 137 are essential for Snail stability, functional cooperation with LOXL2/3 and induction of EMT [15].
  • It is interesting that paricalcitol almost completely suppressed renal induction of Snail, a critical transcription factor that is implicated in EMT programming [16].
  • Here we are the first to report that there is an inverse correlation between Snail and E-cadherin expression in HCC cells as well [17].
  • We recently reported that the SNARE protein SNAP-25 regulates Ca(2+)- activated (K(Ca)) and delays rectifier K(+) channels (K(V)) in oesophageal smooth muscle cells [18].

Co-localisations of Snai1

  • Endogenous NCS-1 was partially co-localized with the synaptic protein SNAP-25 at the plasma membrane in both cell bodies and processes, but not with the Golgi marker [beta]-COP, an individual coat subunit of the coatomer complex present on Golgi-derived vesicles [19].

Regulatory relationships of Snai1

  • Furthermore, Snail genes are induced by transforming growth factor beta gene (TGF-beta) superfamily members, and TGF-beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype [2].
  • Our results show that Snail is able to control Sox10 expression [20].
  • Interestingly, the addition of BMP-4 induced Slug+ neural crest-like cells surrounding the tube-like structures. mRNAs of Snail and dHand, other markers for neural crest cells, were also expressed by the addition of BMP-4 [21].
  • The transcription factor Snail controls epithelial-mesenchymal transitions (EMT) by repressing E-cadherin expression and other epithelial genes [15].
  • Sequence analysis of the negative control region in the Pactolus promoter suggested potential control by Snail and/or Smad families of transcription regulators [22].
  • FGFR3 requires Snail1 during bone development and disease as the inhibition of Snail1 abolishes its signaling even through achondroplastic- and thanatophoric-activating FGFR3 forms [23].

Other interactions of Snai1


Analytical, diagnostic and therapeutic context of Snai1


  1. Generation of a Snail1 (Snai1) conditional null allele. Murray, S.A., Carver, E.A., Gridley, T. Genesis (2006) [Pubmed]
  2. Snail family members and cell survival in physiological and pathological cleft palates. Martínez-Alvarez, C., Blanco, M.J., Pérez, R., Rabadán, M.A., Aparicio, M., Resel, E., Martínez, T., Nieto, M.A. Dev. Biol. (2004) [Pubmed]
  3. Snail blocks the cell cycle and confers resistance to cell death. Vega, S., Morales, A.V., Ocaña, O.H., Valdés, F., Fabregat, I., Nieto, M.A. Genes Dev. (2004) [Pubmed]
  4. The transcriptional repressor Snail promotes mammary tumor recurrence. Moody, S.E., Perez, D., Pan, T.C., Sarkisian, C.J., Portocarrero, C.P., Sterner, C.J., Notorfrancesco, K.L., Cardiff, R.D., Chodosh, L.A. Cancer Cell (2005) [Pubmed]
  5. Expression of Snail protein in tumor-stroma interface. Francí, C., Takkunen, M., Dave, N., Alameda, F., Gómez, S., Rodríguez, R., Escrivà, M., Montserrat-Sentís, B., Baró, T., Garrido, M., Bonilla, F., Virtanen, I., García de Herreros, A. Oncogene (2006) [Pubmed]
  6. Multiple functions of Snail family genes during palate development in mice. Murray, S.A., Oram, K.F., Gridley, T. Development (2007) [Pubmed]
  7. Regulation of Twist, Snail, and Id1 is conserved between the developing murine palate and tooth. Rice, R., Thesleff, I., Rice, D.P. Dev. Dyn. (2005) [Pubmed]
  8. Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission. Raber, J., Mehta, P.P., Kreifeldt, M., Parsons, L.H., Weiss, F., Bloom, F.E., Wilson, M.C. J. Neurochem. (1997) [Pubmed]
  9. The snail superfamily of zinc-finger transcription factors. Nieto, M.A. Nat. Rev. Mol. Cell Biol. (2002) [Pubmed]
  10. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Cano, A., Pérez-Moreno, M.A., Rodrigo, I., Locascio, A., Blanco, M.J., del Barrio, M.G., Portillo, F., Nieto, M.A. Nat. Cell Biol. (2000) [Pubmed]
  11. Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo. Sefton, M., Sánchez, S., Nieto, M.A. Development (1998) [Pubmed]
  12. Snail induction is an early response to Gli1 that determines the efficiency of epithelial transformation. Li, X., Deng, W., Nail, C.D., Bailey, S.K., Kraus, M.H., Ruppert, J.M., Lobo-Ruppert, S.M. Oncogene (2006) [Pubmed]
  13. Snail1 gene function during early embryo patterning in mice. Murray, S.A., Gridley, T. Cell Cycle (2006) [Pubmed]
  14. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Carver, E.A., Jiang, R., Lan, Y., Oram, K.F., Gridley, T. Mol. Cell. Biol. (2001) [Pubmed]
  15. A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. Peinado, H., Del Carmen Iglesias-de la Cruz, M., Olmeda, D., Csiszar, K., Fong, K.S., Vega, S., Nieto, M.A., Cano, A., Portillo, F. EMBO J. (2005) [Pubmed]
  16. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. Tan, X., Li, Y., Liu, Y. J. Am. Soc. Nephrol. (2006) [Pubmed]
  17. Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Jiao, W., Miyazaki, K., Kitajima, Y. Br. J. Cancer (2002) [Pubmed]
  18. Distinct regional expression of SNARE proteins in the feline oesophagus. Ji, J., Lau, H., Sheu, L., Diamant, N.E., Gaisano, H.Y. Neurogastroenterol. Motil. (2002) [Pubmed]
  19. Overexpression of rat neuronal calcium sensor-1 in rodent NG108-15 cells enhances synapse formation and transmission. Chen, X.L., Zhong, Z.G., Yokoyama, S., Bark, C., Meister, B., Berggren, P.O., Roder, J., Higashida, H., Jeromin, A. J. Physiol. (Lond.) (2001) [Pubmed]
  20. Sox10 is required for the early development of the prospective neural crest in Xenopus embryos. Honoré, S.M., Aybar, M.J., Mayor, R. Dev. Biol. (2003) [Pubmed]
  21. Noggin and basic FGF were implicated in forebrain fate and caudal fate, respectively, of the neural tube-like structures emerging in mouse ES cell culture. Chiba, S., Kurokawa, M.S., Yoshikawa, H., Ikeda, R., Takeno, M., Tadokoro, M., Sekino, H., Hashimoto, T., Suzuki, N. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2005) [Pubmed]
  22. Transcriptional control of Pactolus: evidence of a negative control region and comparison with its evolutionary paralogue, CD18 (beta2 integrin). Hale, J.S., Dahlem, T.J., Margraf, R.L., Debnath, I., Weis, J.J., Weis, J.H. J. Leukoc. Biol. (2006) [Pubmed]
  23. Snail1 is a transcriptional effector of FGFR3 signaling during chondrogenesis and achondroplasias. de Frutos, C.A., Vega, S., Manzanares, M., Flores, J.M., Huertas, H., Martínez-Frías, M.L., Nieto, M.A. Dev. Cell (2007) [Pubmed]
  24. Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan. Seki, K., Fujimori, T., Savagner, P., Hata, A., Aikawa, T., Ogata, N., Nabeshima, Y., Kaechoong, L. J. Biol. Chem. (2003) [Pubmed]
  25. The transcriptional control of trunk neural crest induction, survival, and delamination. Cheung, M., Chaboissier, M.C., Mynett, A., Hirst, E., Schedl, A., Briscoe, J. Dev. Cell (2005) [Pubmed]
  26. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dale, J.K., Malapert, P., Chal, J., Vilhais-Neto, G., Maroto, M., Johnson, T., Jayasinghe, S., Trainor, P., Herrmann, B., Pourquié, O. Dev. Cell (2006) [Pubmed]
  27. Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene. Nieto, M.A., Bennett, M.F., Sargent, M.G., Wilkinson, D.G. Development (1992) [Pubmed]
  28. Snail is an immediate early target gene of parathyroid hormone related peptide signaling in parietal endoderm formation. Veltmaat, J.M., Orelio, C.C., Ward-Van Oostwaard, D., Van Rooijen, M.A., Mummery, C.L., Defize, L.H. Int. J. Dev. Biol. (2000) [Pubmed]
  29. Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail. Kim, H.J., Litzenburger, B.C., Cui, X., Delgado, D.A., Grabiner, B.C., Lin, X., Lewis, M.T., Gottardis, M.M., Wong, T.W., Attar, R.M., Carboni, J.M., Lee, A.V. Mol. Cell. Biol. (2007) [Pubmed]
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