Coordination of Cell Proliferation and Cell Fate Determination by CES-1 Snail

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. © 2013 yan et al.