REGULATION OF NEURON PRODUCTION IN CEREBRAL CORTEX

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Normal development of the cerebral cortex, including appropriate regionalization, is required for higher sensory and cognitive functions. One would predict that interference in the normal development could result in, for example, cognitive deficits or mental retardation observed in many congenital birth defects affecting the central nervous system. Furthermore, there is increasing evidence that developmental defects may even underlie disorders bat are first manifested later in life. These studies focus on the expression of the c-myc intron binding protein (mibp1) during the earliest phase of cerebral cortex development, just as progenitors begin to differentiate into neurons. In preliminary studies, we show that mibpl is transiently expressed at the beginning of neurogenesis, mibpl requires an extra-cortical signal to initiate its expression, and that the onset of mibpl expression is prevented n vivo with antisense oligonucleotides. We propose experiments to test the hypothesis that mibpl controls the onset of neuron production in the cerebral cortex. The ability to manipulate neuron production, and later generate animals with abnormal cortical development, will provide models to test how modest defects at the molecular level an lead to long-term abnormalities.