During C. elegans neurogenesis, the NSM cells differentiate into serotonergic neurons while their sister cells undergo programmed cell death(PCD). On p. 4057,Thellmann et al. show that transcriptional regulation of the most upstream gene in the C. elegans central cell-death pathway - the cell-death activator gene egl-1 - is involved in this PCD event. They also define a regulatory element that is required for egl-1 expression. Their findings show that the SNAIL-like protein, CES-1, which blocks NSM sister cell death, and a heterodimer of the helix-loop-helix proteins, HLH-2 and HLH-3, which is required for NSM sister PCD, both bind to this regulatory element. The authors propose that HLH-2/HLH-3 is a cell-type specific activator of egl-1 transcription and suggest that CES-1 and HLH-2/HLH-3 determine NSM sister cell fate by competing to bind to the egl-1 locus.

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