The p38 mitogen-activated protein kinase (MAPK) pathway is involved in many important cellular processes, including cell growth, cell survival and immune response. Previous work done in our lab shows that p38 pathway plays an important role in early development in zebrafish. p38 MAP kinase activates MAP-kinase-activated protein kinase (MK2)/betty boop (bbp). Embryos from mutant mk2a/bbp females undergo dramatic constriction and lysis of yolk cell at 50% epiboly. Preliminary data from this project suggests that mk2a negatively regulates the activity of zebrafish homolog of an RNA binding protein Tristetraprolin (TTP), which in turn regulates mRNA degradation and translational repression of target mRNAs by binding to AU-rich elements (AREs) in the 3’ untranslated region (UTR). We have identified putative TTP targets expressed in the yolk cell and have developed an in vivo assay to investigate the regulation of gene expression by elements in the 3’ UTR.
MK2/TTP pathway is not required for early development in mammals. Instead, it’s involved in inflammatory response by regulating production of important immune modulators like TNF- α and GM-CSF. Embryonic zebrafish offers unique advantages over other systems, including the transparency of larvae and the lack of adaptive immune responses for the first few weeks after hatching. Here, we use zebrafish as a model to explore the role of MK2/TTP in regulation of different components of innate immunity in their interaction with the fungus Candida albicans.
We hypothesize that the ancestral role of MK2 in innate immunity is conserved and that a novel function in regulating yolk cell gene expression evolved within the actinopterygian linage to regulate gene expression in the newly evolved yolk cell.