Gene and growth factor regulation of neurogenesis during mammalian brain development, with a focus on models of human neurodevelopmental disorders, including autism, schizophrenia and environmental teratogens. One direction of research explores the roles of extracellular growth factors, such as IGF1, bFGF and PACAP, in regulating proliferation of neural precursors in cerebral cortex, hippocampus and cerebellum, working via cell cycle machinery, especially cyclin-dependent kinase inhibitors. Another area of interest examines the effects of environmental teratogens, including methylmercury and neurotherapeutic valproic acid, on neural stem cell proliferation in prenatal cortex and postnatal hippocampus, defining effects on proliferation and programmed cell death, as well as neurogenesis and behavioral consequences. Finally, we are defining the roles of the autism-associated gene, Engrailed 2, in development of cerebellum and hindbrain, as well as secondary effects on forebrain structure and functions. These studies are performed in neural stem cell cultures, and in embryonic and postnatal rodent brains, altering growth factors, genes and microRNAs by using knock out technology, gene over/under expression methods (transfection, in utero electroporation) and pharmacological approaches with subsequent analyses of mRNAs, proteins, cell and tissue morphology and animal behaviors.
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