Biological Potential of a Functional Human SNAILRetrogene

Locascio, Annamaria; Vega, Sonia; Frutos, Cristina A. de; Manzanares, Miguel; Nieto, M. Ángela

doi:10.1074/jbc.m205358200

Cited by 26 publications

(31 citation statements)

References 45 publications

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“…mRNA of the unc-80 orthologue is reported to be enriched in neural tissue in both mouse and human (28,29). Our promoter analysis suggests that unc-79 and unc-80 are co-expressed in neurons, consistent with the overlapping neural expression of their mouse orthologues (28).…”

Section: Discussionsupporting

confidence: 56%

Genetic analysis of crawling and swimming locomotory patterns in C. elegans

Pierce-Shimomura

Chen

Mun

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

259

280

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Alternative patterns of neural activity drive different rhythmic locomotory patterns in both invertebrates and mammals. The neuro-molecular mechanisms responsible for the expression of rhythmic behavioral patterns are poorly understood. Here we show that Caenorhabditis elegans switches between distinct forms of locomotion, or crawling versus swimming, when transitioning between solid and liquid environments. These forms of locomotion are distinguished by distinct kinematics and different underlying patterns of neuromuscular activity, as determined by in vivo calcium imaging. The expression of swimming versus crawling rhythms is regulated by sensory input. In a screen for mutants that are defective in transitioning between crawl and swim behavior, we identified unc-79 and unc-80, two mutants known to be defective in NCA ion channel stabilization. Genetic and behavioral analyses suggest that the NCA channels enable the transition to rapid rhythmic behaviors in C. elegans. unc-79, unc-80, and the NCA channels represent a conserved set of genes critical for behavioral pattern generation.neural rhythms ͉ neurogenetics ͉ sodium leak channel D ifferent forms of rhythmic neural output are ubiquitously observed in motor behaviors such as locomotion, respiration, and feeding (1-4). Extensive research has revealed that a neural network can switch among alternate rhythms by altering the properties of specific intrinsic membrane currents and synapses (5). Consistent with this framework, some proteins appear to contribute more to the generation of one rhythm than other rhythms. For instance, channels that carry the persistent sodium current appear to be important for gasping but not the normal respiratory rhythm when studied in vitro (6). Physiological approaches are sometimes limited when trying to identify specific proteins involved in certain rhythms, however, because of the availability and selectivity of compounds that act on the relevant molecules. With the advent of reverse genetics, these limitations are beginning to be overcome by knocking out or modifying specific genes (7, 8), but both pharmacological and gene manipulation approaches are still limited by the a priori hypotheses on which molecules to target. In contrast, because forward genetic studies are unbiased, they can lead to the identification of novel or uncharacterized proteins that contribute to rhythmic neural output. We have therefore pursued a forward genetic approach to identify neural proteins that contribute more to the generation of one form of rhythmic locomotion (i.e., swimming) than another (i.e., crawling) in the nematode Caenorhabditis elegans.C. elegans moves by generating waves of dorsal-ventral (DV) bends along its body. Prior genetic studies have focused on the molecular mechanisms responsible for crawling over a solid agar substrate (9, 10), whereas the motion C. elegans displays in liquid has only begun to be characterized (11). Although C. elegans encounters water in its natural environment (12), it has been unclear whether its motion i...

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Section: Discussionsupporting

confidence: 56%

Genetic analysis of crawling and swimming locomotory patterns in C. elegans

Pierce-Shimomura

Chen

Mun

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

259

280

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“…According to our results, this fragment can function as an active promoter and direct the expression of SNA1P. This can explain why expression of SNAIP retrogene has been observed in different tissues (Locascio et al, 2002). However, the lack of sites of alternative initiation of transcription at À162 or upstream leaves the question of the generation of this retrogene still unexplained.…”

Section: Discussionmentioning

confidence: 88%

Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells

et al. 2004

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Expression of Snail transcriptional factor is a determinant in the acquisition of a mesenchymal phenotype by epithelial tumor cells. However, the regulation of the transcription of this gene is still unknown. We describe here the characterization of a human SNAIL promoter that contains the initiation of transcription and regulates the expression of this gene in tumor cells. This promoter was activated in cell lines in response to agents that induce Snail transcription and the mesenchymal phenotype, as addition of the phorbol ester PMA or overexpression of integrin-linked kinase (ILK) or oncogenes such as Ha-ras or v-Akt. Although other regions of the promoter were required for a complete stimulation by Akt or ILK, a minimal fragment (À78/ þ 59) was sufficient to maintain the mesenchymal specificity. Activity of this minimal promoter and SNAIL RNA levels were dependent on ERK signaling pathway. NFjB/p65 also stimulated SNAIL transcription through a region located immediately upstream the minimal promoter, between À194 and À78. These results indicate that Snail transcription is driven by signaling pathways known to induce epithelial to mesenchymal transition, reinforcing the role of Snail in this process.

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“…Reduced E-cadherin expression has been shown to cause cellular morphological changes in epithelial cells, resulting in a more fibroblastic and flattened phenotype (Frixen et al, 1991;Vleminckx et al, 1991;Batlle et al, 2000;Cano et al, 2000;Poser et al, 2001;Savagner, 2001;Blanco et al, 2002;Hajra et al, 2002;Locascio et al, 2002;Nieto, 2002;Rosivatz et al, 2002;Thiery, 2002). Recent reports have demonstrated E-cadherin expression in some sarcomas, mainly SS, particularly in the glandular structures of biphasic SS (Sato et al, 1999;Saito et al, 2000;Laskin and Miettinen, 2002;Yoo et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the loss of E-cadherin expression is involved in the invasive and metastatic properties of neoplastic cells (Takeichi, 1991(Takeichi, , 1993Mayer et al, 1993;Hirohashi, 1998). In addition, downregulation of E-cadherin has also been reported to occur during epithelial-mesenchymal transitions, the process of cellular morphological changes in epithelial cells from epithelial features to a more fibroblastic and flattened phenotype (Batlle et al, 2000;Cano et al, 2000;Poser et al, 2001;Savagner, 2001;Blanco et al, 2002;Hajra et al, 2002;Locascio et al, 2002;Nieto, 2002;Rosivatz et al, 2002;Thiery, 2002).…”

Section: Introductionmentioning

confidence: 99%