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Cytokine regulation of neuronal differentiation of hippocampal progenitor cells.
Cytokine regulation of neuronal differentiation of hippocampal progenitor cells.
- Source :
-
Nature [Nature] 1993 Mar 04; Vol. 362 (6415), pp. 62-5. - Publication Year :
- 1993
-
Abstract
- The signalling mechanisms governing haematolymphopoiesis and those regulating neural development may be closely related, as indicated by similarities of higher-order structure and function of the cytokines involved, of the regional and temporal regulation of their transcription and translation, and of their bioactivity. Here we investigate this possible evolutionary connection using retroviral transduction of a temperature-sensitive mutant form of the SV40 large T antigen to develop conditionally immortalized murine embryonic hippocampal progenitor cell lines. Treatment of these cells with cytokines that are thought to participate in progressive lymphoid maturation, immunoglobulin synthesis and erythropoiesis causes progressive neuronal differentiation, as defined by morphological criteria, successive expression of increasingly mature neurofilament protein, and the generation of inward currents and action potentials. The cytokine interleukin(IL)-11 induces expression of action potentials that are insensitive to tetrodotoxin, which is indicative of developmentally immature sodium channels. By contrast, for expression of more mature action potentials (tetrodotoxin-sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-alpha after pretreatment with basic fibroblast growth factor. Our results suggest that the mechanisms regulating lineage commitment and cellular differentiation in the neural and haematopoietic systems are similar. Further, they define an in vitro model system that may facilitate molecular analysis of graded stages of mammalian neuronal differentiation.
- Subjects :
- Action Potentials drug effects
Animals
Antigens, Polyomavirus Transforming genetics
Cell Differentiation drug effects
Cell Differentiation physiology
Cell Line, Transformed
Cells, Cultured
Embryo, Mammalian
Fibroblast Growth Factor 2 pharmacology
Hippocampus physiology
Interleukin-11 pharmacology
Interleukin-5 pharmacology
Interleukin-7 pharmacology
Interleukin-9 pharmacology
Mice
Neurons drug effects
Neurons physiology
Simian virus 40 genetics
Stem Cells drug effects
Stem Cells physiology
Tetrodotoxin pharmacology
Transforming Growth Factor alpha pharmacology
Cytokines pharmacology
Hippocampus cytology
Interleukins pharmacology
Neurons cytology
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 362
- Issue :
- 6415
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 8383296
- Full Text :
- https://doi.org/10.1038/362062a0