NEURO-GLIAL NEUROTROPHIC INTERACTION IN THE S-100-BETA RETARDED MUTANT MOUSE (POLYDACTYLY-NAGOYA) .2. COCULTURES STUDY

The homozygote of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) shows several brain abnormalities, and significant decrease of S-100 beta in the brain [17]. An accompanying paper [18] demonstrates that the hippocampus and caudo-dorsal cortex of homozygote (Pdn/Pdn) mouse were markedly reduced in S-100 beta positive astrocytes and serotonergic fibers, and the content of 5-HT and 5-HIAA of hippocampus and cortex of Pdn/Pdn mouse was lower than those of heterozygote (Pdn/+) or wild type (+/+) mice. To further clarify the effects of target tissues from different type brains on the development of serotonergic neurons, raphe neurons from Pdn/Pdn or +/+ newborn mice were co-cultured with hippocampus or cortex of +/+ or Pdn/Pdn newborn mice. The growth of the serotonergic neurons in the mesencephalic raphe tissue dissociated cultures was estimated by measuring the specific uptake of [H-3]5-HT. The development of both genotypes (Pdn/Pdn and +/+) of serotonergic neurons was enhanced by co-cultures with target tissues (hippocampus and cortex) of +/+ brain. This effect was not observed in the co-cultures with Pdn/Pdn brain as a source of target tissue. The present results support the idea that the developmental defect of serotonergic fibers in the Pdn mutant mouse is caused by the deficiency of S-100 beta in the astrocyte of this mutant, and suggest that S-100 beta is a serotonergic growth factor. This mutant mouse is a useful in vivo model to study neural-glial neurotrophic interactions.