Amro Hamdoun
National Institutes of Health Postdoctoral Fellow, Stanford University, Hopkins Marine Station

The Cellular Toolkit for Development in Real-World Environments: How Embryos Keep Toxicants Out

Abstract

Contrary to the view of embryos as life's most fragile stage, embryos possess robust buffering and protection mechanisms.  This buffering of development occurs via action of a cellular toolkit that neutralizes environmental stressors and stabilizes developmental networks. As part of the annotation of the sea urchin, Strongylocentrotus purpuratus, genome we have identified the major genes in this cellular toolkit, which we term the defensome. These genes provide cellular protection against heat, oxidative damage, toxicants and other environmental stressors that embryos might encounter during development. I have focused on the major mechanism of toxicant defense in embryos, the multidrug efflux transporters. I found that at least two types of transporters are already present in sea urchin eggs before fertilization. Their activity turns on 30 minutes after fertilization and the major activity results from a multidrug resistance (mrp/ABCC)-type protein. The early activation involves redistribution of the existing stores of transporters and movement to the membrane. This efflux activity serves two functions; it protects the embryo from xenotoxicants and appears involved in regulation of cell cycle progression. As one indication of their importance in sea urchins, the ABCC family of genes is at least 2-fold larger than orthologous families in other animal genomes; another indication of their importance during development is that 25 of the 30 ABCC genes in the genome are expressed during embryonic or larval development. This information is the foundation for functional genomic studies of the ABCC genes in development, using both loss of function (morpholino) and real time in vivo imaging of transporter (GFP fusion) proteins. Two future lines of inquiry are to understand how cellular defenses enhance fitness of embryos and larvae in real-world conditions and to identify man-made toxicants in the environment that are problematic for these defenses.