eor-1 and eor-2 are required for cell-specific apoptotic death in C. elegans

Programmed cell death occurs in every multicellular organism and in diverse cell types yet the genetic controls that define which cells will live and which will die remain poorly understood. During development of the nematode Caenorhabditis elegans, the coordinated activity of four gene products, EGL-1, CED-9, CED-4 and CED-3, results in the death of essentially all cells fated to die. To identify novel upstream components of the cell death pathway, we performed a genetic screen for mutations that abolish the death of the hermaphrodite-specific neurons (HSNs), a homologous pair of cells required for egg-laying in the hermaphrodite. We identified and cloned the genes, eor-1 and eor-2, which are required to specify the fate of cell death in male HSNs. In addition to defects in HSN death, mutation of either gene leads to defects in coordinated movement, neuronal migration, male tail development, and viability; all consistent with abnormal neuronal differentiation. eor-1 encodes a putative transcription factor related to the human oncogene PLZF. eor-2 encodes a novel but conserved protein. We propose that eor-1 and eor-2 function together throughout the nervous system to promote terminal differentiation of neurons and function specifically in male HSNs to promote apoptotic death of the HSNs.