Expression of the major isoforms of three neurexin genes was analyzed in the developing embryonic nervous system of mice by Northern blot and in situ hybridization. Transcripts of all three genes were detected as early as embryonic day 10 (E10) and increased with maturation of the nervous system. RNAs of the major neurexin isoforms (alpha and beta) were found throughout the central nervous system exclusively in postmitotic neurons and at least 1 d before synapses are formed. In contrast, in the PNS the alpha- and beta-isoforms displayed differential expression patterns. Neurexin III mRNA showed a more restricted regional expression than neurexin I and II transcripts. These expression profiles are consistent with the hypothesis that the neurexins have a function in early neuronal differentiation and axogenesis.