Alec Whited / Biology / Faculty Mentor: Piya Ghose
We have previously described a non-canonical apoptotic program in the nematode C. elegans, Compartmentalized Cell Elimination (CCE), through which two complex embryonic cells, an epithelial cell (the tail-spike cell) and a set of sensory neurons, die in a tripartite fashion. From a candidate gene screen, we found that mutants for egl-44, which encodes a transcription enhancer factor of the TEA domain (TEAD) class, have CCE defects. TEADs are key transcription factors of the Hippo pathway, an evolutionarily conserved signaling network that serves in cell proliferation and differentiation, organ growth, embryogenesis, and wound healing. Dysregulation of the Hippo pathway is linked to cancer, and many other diseases. In mammals, the YAP (Yes-associated protein (YAP))/TAZ, also part of the Hippo pathway, are transcriptional coactivators that bind to TEAD 1–4 transcription factors. We found that mutants for C. elegans yap-1 also have CCE defects. Our preliminary genetic data link a highly important signaling pathway to a novel form of cell death. Our future studies include determining the transcriptional target of the EGL-44/TEAD/ YAP-1 module.
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