(682c) A Systems Biology Approach to Central Nervous System Development and the Effects of Prenatal Alcohol Exposure

Authors: 
Staehle, M. M. - Presenter, Rowan University
Vadigepalli, R., Thomas Jefferson University
Sweeney, K., Rowan University
Garrett, J., Rowan University

Prenatal alcohol exposure affects the fetal development of humans leading to a range of neurological and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD).  The specific causes of these effects are largely unknown.  Recent data supports that alcohol exposure in utero affects embryonic stem cells directly, but the kinetics and exact molecular effects of these interactions are poorly understood.  Furthermore, while several mathematical models have been developed to describe the transcription factor network known to maintain pluripotency in embryonic stem cells, these models are unable to predict the changes in this network that result from alcohol exposure.  In this work, we present a new mathematical model that introduces stochasticity and decouples two transcription factors, Oct4 and Sox2, whose balance has been shown experimentally to be altered in mouse embryonic stem cells following alcohol exposure.  This model enables the in silico investigation and comparison of the intrinsic and extrinsic changes necessary to replicate published experimental data, thereby generating potentially testable hypotheses.  In this presentation, we will also discuss a complementary in vivo approach to the systems biology of central nervous system development in which we are studying Schmidtea mediterranea (Smed) planarian flatworms as a model system for FASD.  Smed possess simple central nervous systems and have the remarkable ability to regenerate their bodies, including the nervous system.  We have shown that alcohol exposure during head regeneration induces a delayed reacquisition of cognitive behavior, indicating that alcohol affects the central nervous system redevelopment in this organism.  Taken together, these complementary systems enable a systems biology approach to the study of alcohol’s effects on central nervous system development.