Integrating Morphological and Behavioral Phenotypes in Developing Zebrafish

The zebrafish, with its prolific reproduction, rapid development, and genetic homology to humans, provides an ideal model to efficiently characterize behavioral, developmental, and morphological phenotypes in biomedical research. By designing experiments to take advantage of these properties, behavioral phenotypes can be interpreted within the context of relevant neuromorphological phenotypes in order to present a truly integrative analysis of the rich biological data. These experiments may take the form of targeted studies or scaled up to a discovery mode that can keep pace with in vitro high-throughput screening (HTS) experimental systems. Achieving the goal of data integration will require appropriate application and adaptation of traditional statistical approaches, as well as the development of novel methods implemented in concert with new experimental approaches. In this chapter, we survey experimental designs and statistical methods for behavioral studies in developing zebrafish, then highlight experimental factors and analysis strategies that facilitate integration of morphological and behavioral phenotypes. We conclude that appropriate design and analysis of integrated morphological and behavioral studies using zebrafish can elucidate new chemical bioactivity pathways, identify compounds eliciting a broad range of effects, and paint a more comprehensive picture of development than either class of phenotype alone.