Multiple influences contribute to the terminal state of a cell; namely, its lineage, its position, its intercellular interactions and its pattern of gene expression. The Drosophila determinant of glial cell identity, glial cells missing (gcm), is required as a binary switch between neuronal and glial determination in both the CNS and the PNS. In order to understand better cell fate specification in the nervous system, it is critical to identify sources of regulation of the specific temporal and spatial distribution of gcm. We propose that the sources of regulation of gcm direct glial cell determination in different neural lineages during neurodevelopment. The immediate goal of this research is to identify and analyze the cis-regulatory elements that account for the expression pattern of gcm in the Drosophila embryo. This will be accomplished through a systematic analysis of flanking gcm DNA, using transgenic techniques and homology sequence analysis, in order to identify cis-regulatory enhancer sequences. Upon identification of these cis-acting elements, a determination of putative interacting proteins for these elements will be initiated. To this end, both genetic and biochemical approaches will be executed. This research may strengthen our comprehension of the specification of the progeny of bipotential precursors in the nervous system. Moreover, understanding the mechanism underlying glial cell determination is critical to devising methods to control the regeneration of glia and neurons from neural stem cells, and to combat cancers of the nervous system.
| Waldor, M K; Mitchell, D; Kipps, T J et al. (1987) Importance of immunoglobulin isotype in therapy of experimental autoimmune encephalomyelitis with monoclonal anti-CD4 antibody. J Immunol 139:3660-4 |
