We used both the polymerase chain reaction (PCR) and in situ hybridization to search for the presence of proteolipid protein (PLP) gene transcripts in the developing mouse. Total brain RNA extracted from 13-19-day embryos, analyzed by PCR, demonstrated the presence of a single transcript that was unambiguously identified with the DM-20 mRNA. RNA samples from postnatal day 2 animals also showed a signal corresponding to the PLP transcript, in addition to the DM-20 message. By in situ hybridization of 10-day embryos using a DM-20 antisense cRNA probe, we showed that the localization of the DM-20 message was restricted to the diencephalic basal plate. On the same embryo sections, in addition to the brain localization, an intense hybridizing signal was also detected in the trigeminal and spinal ganglia, the vagal glossopharyngeal ganglion, and the sympathetic ganglion chain. The demonstration of transcription of the PLP gene, long before the beginning of the myelination process, suggests that in addition to a structural function in myelin compaction, some of the products of the PLP gene (DM-20) may have a role during the compartmentalization and differentiation of the neural tube.