N-cadherin specifies first asymmetry in developing neurons

• Published in: The EMBO journal Vol. 31; no. 8; pp. 1893 - 1903
• Main Authors: Gärtner, Annette, Fornasiero, Eugenio F, Munck, Sebastian, Vennekens, Krist'l, Seuntjens, Eve, Huttner, Wieland B, Valtorta, Flavia, Dotti, Carlos G
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 18.04.2012; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: Animals; Brain; Cadherins - metabolism; cell axis orientation; Cell Division; Cell Polarity; Cellular biology; centrosome; Centrosome - metabolism; cortical development; Cytoskeleton - metabolism; Developmental biology; EMBO05; EMBO27; Golgi Apparatus - metabolism; Molecular biology; N-cadherin; Nerve Tissue Proteins - metabolism; Neurites - physiology; neuronal polarity; Neurons; Neurons - physiology; Phosphatidylinositol 3-Kinase - metabolism; Polarization; Rats; N‐cadherin; neuronal polarity; cell axis orientation; centrosome; cortical development
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2012.41

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. Neuronal polarization is determined by localized N‐cadherin expression at one pole of the newborn neuron towards which the Golgi and centrosome move in a PI3K and the actin/microtubule cytoskeleton‐dependent manner.