The genetics of the sexually dimorphic deaths of the C. elegans CEM neutrons

The cells of metazoan organisms possess the capability to commit a form of cellular suicide known as programmed cell death or apoptosis. The proper control of this endogenous death program is essential to animal development and to the prevention of disease. To better understand how individual cells are developmentally specified to die, I studied the survival decision of a single cell type in the nematode Caenorhabditis elegans, the CEM neurons. The CEMs die during hermaphrodite embryogenesis and survive and function as sensory neurons in males. I identified 144 independent mutant strains in which the CEM neurons of hermaphrodites survive, including 52 mutants in known cell-death genes and 67 mutants generally defective sex determination. Another 29 screen isolates displayed a new defect of transcriptional de repression, the green pharynx phenotype. From these isolates and from additional screens, I defined a set of seven genes that function to prevent inappropriate gene expression. From the isolates causing CEM survival I identified two new sex-determination proteins, the PLZF-like transcription factor TRA-4 and the F-box protein SEL-10; demonstrated that the neurogenesis genes vab-3 Pax6 and cnd-1 NeuroD are required for aspects of the CEM fate, including CEM death, and likely function together in this process and in other aspects of C. elegans development, a cooperative relationship likely to be evolutionarily conserved; and identified the Bar family homeodomain transcription factor gene ceh-30 as specifically promoting CEM survival. The CEM neurons of males lacking ceh-30 inappropriately undergo programmed cell death. In the CEMs of hermaphrodites, ceh-30 is directly repressed by TRA-1, a transcription factor that acts as the last step in the sex-determination pathway to promote a hermaphrodite identity.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Schwartz, Hillel Tsvi

Advisor dc:contributor.advisor

• H. Robert Horvitz.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/46626

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/46626