DiBenedetto, Angela

I am an Associate Professor Emeritus in the department of Biology at Villanova University, where my laboratory studies the genetic control of programmed cell death/apoptosis. We have cloned several genes upregulated transcriptionally in rat neurons during developmentally programmed cell death triggered by the removal of nerve growth factor, and are now characterizing these genes molecularly and functionally to determine the role they play in cell death and normal development. One of these genes,mud-6 (message upregulated during death), is the rat homolog of human and mouse Ring3 (nuclear kinase)and Drosophila fsh (female sterile homeotic), a positive regulator of bithorax. These genes define a subfamily of bromo-domain-containing proteins, all of which have been implicated in transcriptional regulation and protein-protein interactions. We have cloned its zebrafish homolog, zmud-6/zRing3, and have established the wild type RNA expression pattern in zebrafish embryos. We are now in the process of testing expression in mutant backgrounds and carrying out knockout studies. We have reason to believe, given what is known of its homologs and given its expression during cell death, that zmud-6 will be an important developmental regulator, possibly through the modification of chromatin structure and/or modulation of groups of other genes.