This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.A key problem in the use of embryonic or adult stem cells in cell replacement therapies for spinal injuries is that the stem cells must be stably converted to distinct, functional cell types before they can have any hope of benefiting affected patients. Brahma-Related Gene-1 (BRG1), which regulates gene expression in cells, is highly expressed in the developing nervous system. We found that loss of Brg1 in the developing nervous system of mutant mice results in animals where all of the neural stem cells appear to abnormally differentiate into neurons. Furthermore, these neurons have altered properties compared to the neurons of normal mice. We believe, therefore, that Brg1 acts as a repressor of neuronal differentiation in stem cell populations and aim, here, to test the possibility that by interfering with Brg1 function or expression, we can generate large numbers of stable neuronal populations from stem cells grown in culture. We further believe that the absence of Brg1 may influence the differentiation and function of certain neuron populations, including spinal motor neurons, once that stem cells turn into neurons. Our long-term aim is to develop reagents that target Brg1 or related proteins as a way of converting stem cells into neurons that could then be used for cell replacement therapies in individuals with spinal injuries.
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