Disruption of blastomeric F-actin: a potential early biomarker of developmental toxicity in zebrafish

The expression of at least some biomarkers of toxicity is generally thought to precede the appearance of frank pathology. In the context of developmental toxicity, certain early indicators may be predictive of later drastic outcome. The search for predictive biomarkers of toxicity in the cells (blastomeres) of an early embryo can benefit from the fact that for normal development to proceed, the maintenance of blastomere cellular integrity during the process of transition from an embryo to a fully functional organism is paramount. Actin microfilaments are integral parts of blastomeres in the developing zebrafish embryo and contribute toward the proper progression of early development (cleavage and epiboly). In early embryos, the filamentous actin (F-actin) is present and helps to define the boundary of each blastomere as they remain adhered to each other. In our studies, we observed that when blastomeric F-actin is depolymerized by agents like gelsolin, the blastomeres lose cellular integrity, which results in abnormal larvae later in development. There are a variety of toxicants that depolymerize F-actin in early mammalian embryos, the later consequences of which are, at present, not known. We propose that very early zebrafish embryos (~5-h old) exposed to such toxicants will also respond in a like manner. In this review, we discuss the potential use of F-actin disruption as a predictive biomarker of developmental toxicity in zebrafish.