Molecular genetic regulation of vertebrate CNS development

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A fundamental issue in our understanding of animal development is how extracellular signaling cues control morphogenesis and cell fate determination in embryos. In many animals, the secreted Hedgehog (Hh) proteins play critical and diverse roles during development and in adults. In humans and mice, Sonic hedgehog (Shh) has an important role in directing pattern formation and inducing progenitor/stem cell division in numerous embryonic tissues, including the central nervous system (CNS), limbs, somites, lungs, gut, teeth, and skin. Previous work in the Matise lab and elsewhere have demonstrated that three Gli transcriptional regulators play a central role in mediating the response to Shh signaling in the vertebrate CNS; however, the transcriptional mechanisms that are responsible for this are poorly understood.The current proposal will address this issue using the developing chicken spinal cord as a model system. The experiments will extend previous NSF-funded work in the Matise lab that demonstrated the normal expression of an identified Shh-Gli target gene also involves proteins dedicated to mediating another signal, the Wnt pathway. Taken with work from other labs, these experiments define what may be a common mechanism for controlling cell fates and tissue patterning that involves the integration of multiple extrinsic positional signaling cues at the level of gene regulation.The proposed studies will be undertaken at a university (UMDNJ/Rutgers) that has a highly diverse student population, and the Matise lab has consistently attracted students who seek training in neuroscience, molecular genetics, and developmental biology. The lab provides an attractive environment for undergraduate and graduate students, and has an excellent history of involving students from under-represented groups. The experimental design and methodology of the proposed experiments is highly approachable, providing an ideal opportunity to train students to apply powerful technologies to study important biological problems. Such training is critical to the continued pre-eminence of the U.S. as a worldwide leader in the advancement of science.