Edward H. Kislauskis

Actin Filaments and the Spatial Positioning of mRNAS

Filamentous actin has been shown to play a major role in the control of mRNA expression. Previous work emphasized RNA-cytoskeletal interactions using biochemical fractionation. More recently, in situ hybridization at the light microscopic and ultrastructural levels has shown that actin, in particular, is directly associated with mRNAs. It is proposed that these interactions play a major regulatory role in how the mRNA is spatially sequestered within the cytoplasm and provide a mechanism for its regulation (Singer, 1992).

Cooperative Regulation of Neurotensin/Neuromedin N Gene Expression in PC12 Cells Involves AP‐1 Transcription Factors

Neurotensin (NT) is widely expressed in the central nervous system with high concentrations of immunoreactive neurons found in the limbic regions of the forebrain. I The regulatory mechanisms underlying the generation of this complex pattern of expression are poorly understood. The regulation of neuronal differentiation has been most extensively studied in the peripheral nervous system, which is derived from the neural crest during embryogenesis.2 Clonal analysis of neural crest cells in culture has provided compelling evidence that neural crest cells are pleuripotent, capable of differentiating into neuronal, endocrine, and a wide variety of other adult cell types (reviewed by Anderson3). The discovery of nerve growth factor (NGF) provided the first evidence that environmental factors play critical roles in the differentiation of crest cells4 The expression of specific neurotransmitters and neuropeptides may require combinations of environmental factors. For instance, cholinergic differentiation factor causes sympathetic neurons to acquire cholinergic traits and can induce the expression of specific ne~ropeptides.5~ Similar regulatory mechanisms could operate in the central nervous system, since cell-tagging experiments indicate that cell lineage does not play a crucial role in the differentiation of central neurons.’ PC12 pheochromocytoma cells differentiate neuronally in response to NGF and have been used extensively as a model for understanding NGF action. In addition to producing the catecholamines norepinephrine and dopamine constitutively, PC12 cells can be induced to synthesize and secrete NT by combinations of NGF, glucocorticoids, and adenylate cyclase activat0rs.Q Subpopulations of catecholaminecontaining cat adrenal medullary cellsI0 and rat central neurons” co-express NT, suggesting that the regulatory mechanisms governing NT expression in PC12 cells may