Early Vertebrate Nervous System Development
Past research in the Stark lab has been focused on cell-fate determination in the early vertebrate nervous system, with a focus on genes that regulate the sensory neuron cell fate. We are currently studying factors involved in neural tube closure, and how various biological compounds act to disrupt this process and cause neural tube defects (NTDs). Ceramide, a modified sphingolipid, has been implicated in disease models of obesity and diabetes, where increased circulating ceramide levels are well-documented (including in pregnant women). The frequency of NTDs is increased in obese pregnancies, however ceramide has not been carefully studied as a causative agent. Ceramide misregulation has been linked to NTDs in women exposed to the known ceramide synthesis inhibitor fumonisin, a corn fungus commonly found in masa. Fumonisin exposure during early pregnancy causes a significant increase in the incidents of NTDs. Our studies utilize the chicken embryo as a model organism. Embryonic exposure to ceramide and/or fumonisin has been shown to induce NTDs in our lab. Our primary focus is to identify the molecular events responsible for failed neurulation in embryos affected by ceramide misregulation.