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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.

The per locus of Drosophila has been implicated in the control of behavioural rhythms. In fruitfly embryos and larvae per is expressed in salivary glands. Per mutations have striking effects on intercellular communication in salivary glands: gap junction channels are modulated so that their conductance varies inversely with the period of behavioural rhythms in the mutants. A similar effect on junctional communication in the nervous system may explain how per influences behavioural rhythms.