Deleted in colorectal cancer (DCC) regulates the migration of luteinizing hormone-releasing hormone neurons to the basal forebrain

Luteinizing hormone-releasing hormone (LHRH) neurons migrate from the vomer onasal organ (VNO) to the forebrain in all mammals studied. In mice, most L HRH neuron migration is dependent on axons that originate in the VNO but by pass the olfactory bulb and project into the basal forebrain. Thus, cues th at regulate the trajectories of these vomeronasal axons are candidates for determining the destination of LHRH neurons. Using in situ hybridization te chniques, we examined the expression of Deleted in colorectal cancer (DCC), a vertebrate receptor for the guidance molecule netrin-1, during developme nt of the olfactory system. DCC is expressed by cells in the olfactory epit helium (OE) and VNO, and in cells migrating from the OE and VNO from embryo nic day 11 (E11) to E14. Some DCC+ cells on vomeronasal axons in the nose a lso express LHRH. However, DCC expression is downregulated beginning at E12 , so few if any LHRH neurons in the forebrain also express DCC. In rat, DCC is expressed on TAG-1(+) axons that guide migrating LHRH neurons. We there fore examined LHRH neuron migration in DCC-/- mice and found that trajector ies of the caudal vomeronasal nerve and positions of LHRH neurons are abnor mal. Fewer than the normal number of LHRH neurons are found in the basal fo rebrain, and many LHRH neurons are displaced into the cerebral cortex of DC C-/- mice. These results are consistent with the idea that DCC regulates th e trajectories of a subset of vomeronasal axons that guide the migration of LHRH neurons. Loss of DCC function results in the migration of many LHRH n eurons to inappropriate destinations.