The research program in this group is in the area of developmental neurobiology. The adult mammalian brain is composed of a vast number of different neurons. In embryonic development, neurons are derived from multipotential precursor cells. When these precursors stop dividing they become committed to give specific neuronal types in a very precise pattern. This commitment step, which occurs in the few hours around the last division, controls critically important features of neuron numbers and types found in the adult brain. Our work is focused on the molecular and cellular mechanisms regulating this process. The key methods we currently employ include: (1) the use of transgenic mice to define DNA sequences that target gene expression to neuronal precursors; (2) dissociated cell and tissue slice culture analysis of growth factors which regulate the proliferation, survival and differentiation of cells in the embryonic brain; and (3) the use of transplanted neuronal precursors to construct chimeric brains carrying genetically engineered functional neurons. These techniques are used to analyze the molecular mechanisms controlling the development and function of the mammalian brain. The results are applicable to understanding the genetic basis of childhood tumors and neurodegenerative diseases of the central nervous system. They may also lead to powerful new therapies to reconstruct the damaged structure(s) found in Parkinson's, Alzheimer's and Huntington's diseases.
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