The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2006-2007

Sea Urchins as an Alternative Animal Model for Testing Drugs and Neurotoxicants as Potential Neuroteratogens

Jean M. Lauder, Ph.D
The University of North Carolina at Chapel Hill

The main goal is to use sea urchin embryos as an alternative animal model to study how exposure to drugs or neurotoxins during pregnancy may cause defects in the developing nervous system. During the first year of funding, a perturb-and-rescue strategy was used to characterize malformations caused by a variety of drugs and neurotoxins, including drugs that target receptors for the brain chemical (neurotransmitter) serotonin, and the neurotoxin, retinoic acid. Results of these studies provided evidence that retinoic acid causes malformations by inhibiting formation of cyclic AMP (cAMP), an important signal regulating cellular development. These malformations can be prevented by drugs that stimulate the cAMP system, like forskolin, or that activate serotonin receptors which promote cAMP synthesis. These results provided the rationale for studies to investigate cellular and molecular mechanisms mediating the opposing actions of retinoic acid and serotonin. The ultimate goal is to use the sea urchin model to test the hypothesis that serotonin opposes retinoid signaling during early stages of development by activating specific receptors and intracellular signaling pathways that promote expression of genes required for the development of specific cell types. Understanding how opposing signaling by retinoic acid and serotonin regulates early sea urchin development could provide important insights into the how the functions of neurotransmitters changed during evolution to allow them to both mediate communication between nerve cells, and act as growth factors for developing cells.

Adult Sea Urchin
Adult Sea Urchin