Cytokine regulation of neuronal differentiation of hippocampal progenitor cells

Mark F. Mehler, Renato Rozental, Maryjane Dougherty, David C. Spray, John A. Kessler

Research output: Contribution to journalArticle

214 Scopus citations

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 involved1, of the regional and temporal regulation of their transcription and translation2-6, and of their bioactivity 7-10. 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 lines11-14. Treatment of these cells with cytokines that are thought to participate in progressive lymphoid maturation, immunoglobulin synthesis15-18 and erythropoiesis19,20 causes progressive neuronal differentiation, as defined by morphological criteria, successive expression of increasingly mature neurofilament proteins21-23, 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 develop-mentally immature sodium channels24. By contrast, for expression of more mature action potentials24 (tetrodotoxin- sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-α 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.

Original languageEnglish (US)
Pages (from-to)62-65
Number of pages4
JournalNature
Volume362
Issue number6415
DOIs
StatePublished - Jan 1 1993

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