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Slit2 Activity in the Migration of Guidepost Neurons Shapes Thalamic Projections during Development and Evolution

Franck Bielle, Paula Marcos-Mondejar, Maryama Keita, Caroline Mailhes, Catherine Verney, Kim Nguyen Ba-Charvet, Marc Tessier-Lavigne, Guillermina Lopez-Bendito and Sonia Garel

How brain connectivity has evolved to integrate the mammalian-specific neocortex remains largely un- known. Here, we address how dorsal thalamic axons, which constitute the main input to the neocortex, are directed internally to their evolutionary novel target in mammals, though they follow an external path to other targets in reptiles and birds. Using comparative studies and functional experiments in chick, we show that local species-specific differences in the migration of previously identified ‘‘corridor’’ guide- post neurons control the opening of a mammalian thalamocortical route. Using in vivo and ex vivo experiments in mice, we further demonstrate that the midline repellent Slit2 orients migration of corridor neurons and thereby switches thalamic axons from an external to a mammalian-specific internal path. Our study reveals that subtle differ- ences in the migration of conserved intermediate target neurons trigger large-scale changes in thalamic connectivity, and opens perspectives on Slit functions and the evolution of brain wiring.


Neuron. 2011 Mar 24;69(6):1085-98.