title: N-cadherin specifies first asymmetry in developing neurons.
abstract: The precise polarization and orientation of developing neurons is essential for the correct wiring of the brain. In pyramidal excitatory neurons, polarization begins with the sprouting of opposite neurites, which later define directed migration and axo-dendritic domains. We here show that endogenous N-cadherin concentrates at one pole of the newborn neuron, from where the first neurite subsequently emerges. Ectopic N-cadherin is sufficient to favour the place of appearance of the first neurite. The Golgi and centrosome move towards this newly formed morphological pole in a second step, which is regulated by PI3K and the actin/microtubule cytoskeleton. Moreover, loss of function experiments in vivo showed that developing neurons with a non-functional N-cadherin misorient their cell axis. These results show that polarization of N-cadherin in the immediate post-mitotic stage is an early and crucial mechanism in neuronal polarity.
authors.affiliation: VIB Center for the Biology of Disease, KULeuven Center for Human Genetics, Leuven, Belgium. Annette.Gaertner@cme.vib-kuleuven.be
authors.forename: Annette
authors.initials: A
authors.lastname: Gärtner
authors.forename: Eugenio F
authors.initials: EF
authors.lastname: Fornasiero
authors.forename: Sebastian
authors.initials: S
authors.lastname: Munck
authors.forename: Krist'l
authors.initials: K
authors.lastname: Vennekens
authors.forename: Eve
authors.initials: E
authors.lastname: Seuntjens
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
authors.forename: Flavia
authors.initials: F
authors.lastname: Valtorta
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002455:Cell Division; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051381:Rats
chemical_list: D015820:Cadherins; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D058539:Phosphatidylinositol 3-Kinase