Neural development requires the generation of an enormous diversity of distinct cell types, and the early assumption of individual cell fates in large part controls the subsequent development of the nervous system. A large body of evidence, from work in Drosophila, C. elegans, and mammalian systems, has suggested that transcription factors of the POU domain family play a central role in the initial commitment to specific cellular lineages, in the transactivation and repression of neural- specific genes, and in the terminal differentiation and function of neural cells. We wish to understand the role of one particular POU domain protein, specifically with regard to the determination of neural cell fate and the timing of neural cell differentiation. This transcription factor - designated SCIP - is transiently expressed by differentiating Schwann cells, oligodendrocytes, and a subset of central nervous system neurons. It is hypothesized that initial activation of the SCIP gene is required for lineage commitment in these cells, and that a subsequent deactivation of this gene is necessary in order for these cells to terminally differentiate. To dissect SCIP function in the developing nervous system, we propose to generate and analyze conditional knock-outs of the mouse SCIP gene in neurons and glia, and to identify, clone, and analyze transcriptional co-factors essential for SCIP action. We also propose to use antibodies to SCIP to define developmental stages of the mammalian Schwann cell lineage. We hope through these experiments to elucidate fundamental mechanisms underlying POU domain regulation of the development of neurons and glia.
| Krappa, R; Nguyen, A; Burrola, P et al. (1999) Evectins: vesicular proteins that carry a pleckstrin homology domain and localize to post-Golgi membranes. Proc Natl Acad Sci U S A 96:4633-8 |
