Abstract
The coordination of cell proliferation and cell fate determination is critical during development but the mechanisms through which this is accomplished are unclear. We present evidence that the Snail-related transcription factor CES-1 of Caenorhabditis elegans coordinates these processes in a specific cell lineage. CES-1 can cause loss of cell polarity in the NSM neuroblast. By repressing the transcription of the BH3-only gene egl-1, CES-1 can also suppress apoptosis in the daughters of the NSM neuroblasts. We now demonstrate that CES-1 also affects cell cycle progression in this lineage. Specifically, we found that CES-1 can repress the transcription of the cdc-25.2 gene, which encodes a Cdc25-like phosphatase, thereby enhancing the block in NSM neuroblast division caused by the partial loss of cya-1, which encodes Cyclin A. Our results indicate that CDC-25.2 and CYA-1 control specific cell divisions and that the over-expression of the ces-1 gene leads to incorrect regulation of this functional ‘module’. Finally, we provide evidence that dnj-11 MIDA1 not only regulate CES-1 activity in the context of cell polarity and apoptosis but also in the context of cell cycle progression. In mammals, the over-expression of Snail-related genes has been implicated in tumorigenesis. Our findings support the notion that the oncogenic potential of Snail-related transcription factors lies in their capability to, simultaneously, affect cell cycle progression, cell polarity and apoptosis and, hence, the coordination of cell proliferation and cell fate determination.
Highlights
Members of the Snail superfamily of zinc-finger transcription factors are essential during development and their deregulation has been implicated in various malignancies including tumorigenesis [1,2,3,4]
Snail-related transcription factors have previously been shown to be involved in the regulation of cell proliferation and cell fate determination
We propose that CES-1 is an important coordinator that is involved in the precise control - in space (NSM lineage) and time (,150 min) - of processes that are critical for animal development
Summary
Members of the Snail superfamily of zinc-finger transcription factors are essential during development and their deregulation has been implicated in various malignancies including tumorigenesis [1,2,3,4]. One of the best known functions of Snail-related proteins is their role in the induction of epithelial-mesenchymal transitions (EMTs) [1,2,4,5]. Hallmarks of EMTs are the loss of apico-basal polarity and adhesive properties, which is critical for the ability of epithelial cells to become migratory. Snail-related proteins contribute to these cellular changes by repressing the transcription of genes that encode factors required for apico-basal polarity and cell adhesion, such as Crumbs and E-cadherin, respectively [6,7,8]
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