To gain a better understanding of the role of DCC and Neogenin in neural and nonneural tissues during vertebrate development we have carried out in situ hybridization studies to determine their expression patterns throughout the mid to late stages of mouse embryogenesis. This analysis revealed striking contrasts in both the spatial and temporal expression patterns of these closely related molecules. While DCC mRNA expression was predominantly restricted to the developing central nervous system (CNS), Neogenin mRNA was detected in a broad spectrum of embryonic tissues. Outside the CNS, Neogenin expression was observed mainly in mesodermal derivatives such as organ primordia and cartilage condensations of many developing embryonic structures. Within the CNS, initiation of DCC expression correlated with the onset of neurogenesis and was maintained at high levels in all regions of the developing CNS actively undergoing neurogenesis. By E18.5, DCC expression was detected only in structures such as the olfactory bulb, the hippocampus, and the cerebellum, that are known to sustain active neurogenesis well into postnatal life. In contrast, Neogenin expression was weak in the early developing CNS but broadened and intensified as neurogenesis proceeded. In summary, these observations indicate that Neogenin is the predominant member of this subfamily in mesodermal tissues, while DCC and Neogenin may play complementary roles in the generation of the fully functional CNS.