In recent years, glial precursor cells surviving in cultures from neonatal rat optic nerve and forebrain have been partially characterized by cell morphology and immunocytochemical markers as they progress along their developmental trajectories. As a result, glial progenitor cultures have become a valuable model of cellular development and differentiation. A number of growth factors have been identified that regulate glial development. These extracellular signals activate a variety of intracellular pathways that can lead to proteins or protein complexes binding to target genes. Thus, extracellular signals triggering intracellular cascades can lead to a selected pattern of transcriptional events and gene expression during cellular differentiation. Recently, an entire family of genes, many encoding for nuclear proteins, has been identified which are induced with very rapid kinetics. Since these immediate-early or early response genes (ERGs) are regulated by the same growth factors which control the proliferation and differentiation of glial cells, we suggest they may be important components of the molecular mechanism that coordinates the regulation of specific genes necessary for normal glial growth and differentiation. We propose utilizing our laboratory's expertise in the molecular and biochemical analysis of glial development to study the pattern of early gene expression in cultures of glial progenitor cells that are progressing along a specific developmental lineage. This research will provide important data concerning the responsiveness of both developing and regenerating glial cells to extracellular signals. As such, our understanding of neural development and repair will be enhanced and potentially lead to new therapeutic approaches to neurodegenerative diseases.
| Tzeng, S F; Kahn, M; Liva, S et al. (1999) Tumor necrosis factor-alpha regulation of the Id gene family in astrocytes and microglia during CNS inflammatory injury. Glia 26:139-52 |
| Tzeng, S F; de Vellis, J (1998) Id1, Id2, and Id3 gene expression in neural cells during development. Glia 24:372-81 |
| Tzeng, S F; de Vellis, J (1997) Expression and functional role of the Id HLH family in cultured astrocytes. Brain Res Mol Brain Res 46:136-42 |
| Arenander, A; de Vellis, J (1992) Early response gene induction in astrocytes as a mechanism for encoding and integrating neuronal signals. Prog Brain Res 94:177-88 |
