Netrin 1 regulates ventral tangential migration of guidepost neurons in the lateral olfactory tract.
In the developing nervous system, functional neural networks are constructed with intricate coordination of neuronal migrations and axonal projections. We have previously reported a ventral tangential migration of a special type of cortical neurons, lot cells, in the mouse embryo. These neurons originate from the ventricular zone of the entire neocortex, tangentially migrate in the surface layer of the neocortex into the ventral direction, align in the future pathway of the lateral olfactory tract (LOT) and eventually guide the projection of LOT axons. In this study, we developed an organotypic culture system to investigate the regulation of this cell migration in the developing telencephalon. Our data show that the neocortex contains the signals that direct lot cells ventrally, that the ganglionic eminence excludes lot cells by repelling the migration and that lot cells are attracted to netrin 1, an axon guidance factor. Furthermore, we demonstrate that mutations in the genes encoding netrin 1 and its functional receptor Dcc lead to inappropriate distribution of lot cells and subsequent partial disruption of LOT projection. These results suggest that netrin 1 regulates the migration of lot cells and LOT projections, possibly by ensuring the correct distribution of these guidepost neurons.
Kawasaki
Takahiko
T
Division of Brain Function, National Institute of Genetics, Graduate University for Advanced Studies, SOKENDAI, Yata 1111, Mishima 411-8540, Japan.
Ito
Keisuke
K
Hirata
Tatsumi
T
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D000075389:DCC Receptor; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009924:Organ Culture Techniques; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000074290:Zinc Finger Protein Gli3
D000075389:DCC Receptor; C501910:Dcc protein, mouse; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000074290:Zinc Finger Protein Gli3; D000075388:Netrin-1