PMID- 10341242 OWN - NLM STAT- MEDLINE DCOM- 19990616 LR - 20191023 IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 19 IP - 11 DP - 1999 Jun 1 TI - Floor plate and netrin-1 are involved in the migration and survival of inferior olivary neurons. PG - 4407-20 AB - During their circumferential migration, the nuclei of inferior olivary neurons translocate within their axons until they reach the floor plate where they stop, although their axons have already crossed the midline to project to the contralateral cerebellum. Signals released by the floor plate, including netrin-1, have been implicated in promoting axonal growth and chemoattraction during axonal pathfinding in different midline crossing systems. In the present study, we report experiments that strongly suggest that the floor plate could also be involved in the migration of inferior olivary neurons. First, we show that the pattern of expression of netrin receptors DCC (for deleted in colorectal cancer), neogenin (a DCC-related protein), and members of the Unc5 family in wild-type mice is consistent with a possible role of netrins in directing the migration of precerebellar neurons from the rhombic lips. Second, we have studied mice deficient in netrin-1 production. In these mice, the number of inferior olivary neurons is remarkably decreased. Some of them are located ectopically along the migration stream, whereas the others are located medioventrally and form an atrophic inferior olivary complex: most subnuclei are missing. However, axons of the remaining olivary cell bodies located in the vicinity of the floor plate still succeed in entering their target, the cerebellum, but they establish an ipsilateral projection instead of the normal contralateral projection. In vitro experiments involving ablations of the midline show a fusion of the two olivary masses normally located on either side of the ventral midline, suggesting that the floor plate may function as a specific stop signal for inferior olivary neurons. These results establish a requirement for netrin-1 in the migration of inferior olivary neurons and suggest that it may function as a specific guidance cue for the initial steps of the migration from the rhombic lips and then later in the development of the normal crossed projection of the inferior olivary neurons. They also establish a requirement for netrin-1, either directly or indirectly, for the survival of inferior olivary neurons. FAU - Bloch-Gallego, E AU - Bloch-Gallego E AD - Institut National de la Sante et de la Recherche Medicale U106, Hopital de la Salpetriere, 75013 Paris, France. FAU - Ezan, F AU - Ezan F FAU - Tessier-Lavigne, M AU - Tessier-Lavigne M FAU - Sotelo, C AU - Sotelo C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Nerve Growth Factors) RN - 0 (Ntn1 protein, mouse) RN - 0 (Tumor Suppressor Proteins) RN - 158651-98-0 (Netrin-1) SB - IM MH - Animals MH - Animals, Newborn MH - Cell Movement/physiology MH - Cell Survival/physiology MH - Cerebellum/physiology MH - Chick Embryo MH - Mice MH - Mutation MH - Nerve Growth Factors/*physiology MH - Nervous System/*embryology MH - Netrin-1 MH - Neural Pathways/physiology MH - Neurons/cytology/*physiology MH - Olivary Nucleus/cytology/*physiology MH - Organ Culture Techniques MH - Purkinje Cells/physiology MH - Tumor Suppressor Proteins PMC - PMC6782586 EDAT- 1999/05/26 00:00 MHDA- 1999/05/26 00:01 CRDT- 1999/05/26 00:00 PHST- 1999/05/26 00:00 [pubmed] PHST- 1999/05/26 00:01 [medline] PHST- 1999/05/26 00:00 [entrez] PST - ppublish SO - J Neurosci. 1999 Jun 1;19(11):4407-20.