Identification of phenotypic defects in the zinc finger transcription factor ztf-29

Aging and many aging-associated diseases such as Alzheimer’s disease and cancer are characterized by a progressive decline in physiological functions and a decline in the ability to respond to stress. The underlying causes for many aging-associated diseases are unknown. Identifying genes that control normal aging will advance our understanding of the molecular changes that underlie the aging process and might help treat age-associated diseases. In order to get a better understanding of the molecular mechanisms behind these diseases, we utilize the nematode Caenorhabditis elegans as a model organism to examine defects in physiology and aging. The human PRDM genes code for zinc finger transcription factors, and mutations in these genes are associated with mixed lineage leukemia and other cancers. To gain a better understanding of how PRDM genes work at the molecular level and how they interact with other cancer and aging related genes, we examined a mutation in ztf-29, which is the C. elegans ortholog of PRDM16. Using a kal-1-GFP reporter gene, we found that ztf-29 mutants exhibit defects in head neuron positioning, including localization and morphology. We also analyzed ztf-29 mutants for behavioral phenotypes using video tracking, which revealed defects in locomotion including a significant reduction in the average number of reversals performed. Finally, we used a mitochondrial stress reporter gene to determine if ztf-29 has roles in mitochondrial homeostasis. We find that ztf-29 mutants exhibit chronic mitochondrial stress responses, suggesting that ztf-29 may have a role in mitochondrial gene regulation and/or function. Based on these results, we conclude that ztf-29 plays a significant role in C. elegans nervous system development along with the maintenance of mitochondrial physiology. Work is on-going to rescue ztf-29 mutant phenotypes and to gain a better understanding of what other genes ztf-29 might be working with during normal development and physiology