Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation

PMID:16615895Neuronal migration and axon guidance constitute fundamental processes in brain development that are generally studied independently. Although both share common mechanisms of cell biology and biochemistry, little is known about their coordinated integration in the formation of neural circuits. Here we show that the development of the thalamocortical projection, one of the most prominent tracts in the mammalian brain, depends on the early tangential migration of a population of neurons derived from the ventral telencephalon. This tangential migration contributes to the establishment of a permissive corridor that is essential for thalamocortical axon pathfinding. Our results also demonstrate that in this process two different products of the Neuregulin-1 gene, CRD-NRG1 and Ig-NRG1, mediate the guidance of thalamocortical axons. These results show that neuronal tangential migration constitutes a novel mechanism to control the timely arrangement of guidance cues required for axonal tract formation in the mammalian brain.We have been supported by grants from Spanish Government BMC2002-03337, GVA GRUPOS03/053, NARSAD, the European Commission through STREP contract number 005139 (INTERDEVO), and the EURYI program to O.M.; by grants from INSERM, MENRT, ARC, and AFM to P.C.; by NIH grant NS29071 to L.R. and D.T.; and by the Picasso PAI/Programa de Acciones Integradas to O.M. and S.G. G.L.-B. is a “Ramón y Cajal” Investigator from the CSIC. F.B. was supported by a fellowship from the Académie Nationale de Médecine. S.G. is a recipient of the Human Frontier Science Program Organization CDA. O.M. is an EMBO Young Investigator, a NARSAD Young Investigator, and an EURYI Awardee.Peer reviewe