IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration

QUIROGA, SANTIAGO

Scientific Reports

Nature Springer

Lugar: Londres; Año: 2017 vol. 7

uring cortical development, neurons undergo polarization, oriented migration and layer-typedifferentiation. The biological and biochemical mechanisms underlying these processes are notcompletely understood. In neurons in culture we showed that IGF-1 receptor activation is importantfor growth cone assembly and axonal formation. However, the possible roles of the insulin like growthfactor-1 receptor (IGF-1R) on neuronal differentiation and polarization in vivo in mammals have not yetbeen studied. Using in utero electroporation, we show here that the IGF-1R is essential for neocorticaldevelopment. Neurons electroporated with a shRNA targeting IGF-1 receptor failed to migrate to theupper cortical layers and accumulated at the ventricular/subventricular zones. Co-electroporation with aconstitutively active form of PI3K rescued migration. The change of the morphology from multipolar tobipolar cells was also attenuated. Cells lacking the IGF-1 receptor remain arrested as multipolar forminga