1. Cortex development and evolution
Cortical expansion and folding are assumed to be associated with the emergence of uniquely cognitive skills in primates. However, this hypothesis has been mainly based on across species comparative studies. We aim to understand genetic, molecular and cellular basis of cortex expansion, with particular interests on regulations of neural precursors (NPs) by hominoid-specific genes, contribution of NPs to cortex expansion, and the effects of cortical folding on higher brain functions. We are generating genetic modified model animals, including mice and monkeys, to address these questions.
2. Axon growth and guidance
The establishment of functional neural circuits requires precise projection of axons, and the growth of which are guided by various, long-range or short-range, attractive or repulsive cues, including Netrin, Slit, Semaphorin, Ephrin, and Wnt, etc. Based on the complex brain wiring in mammals, we assume the presence of additional guidance cues that remain to be identified. We are using gene expression profiling, primary neuron culture, explants co-culture, microfluid system, in utero electroporation, and axon tract tracing of genetic mutant mice, to validate the function of candidate molecules.
3. Synapse differentiation and pruning
Synapse formation and elimination constitute critical processes in the formation of neural circuits and structural or functional synaptic plasticity underlies neural basis for brain functions. We are interested in key questions as of how the synapse specification is determined, which regulatory mechanisms control specific connections between various types of neurons, and which molecules determine pruning of redundant neural connections during early developmental stages. We are using cell culture system and genetic modified mice to study these questions.