RESUMO
In the mouse trigeminal pathway, sensory inputs from distinct facial structures, such as whiskers or lower jaw and lip, are topographically mapped onto the somatosensory cortex through relay stations in the thalamus and hindbrain. In the developing hindbrain, the mechanisms generating such maps remain elusive. We found that in the principal sensory nucleus, the whisker-related map is contributed by rhombomere 3-derived neurons, whereas the rhombomere 2-derived progeny supply the lower jaw and lip representation. Moreover, early Hoxa2 expression in neuroepithelium prevents the trigeminal nerve from ectopically projecting to the cerebellum, whereas late expression in the principal sensory nucleus promotes selective arborization of whisker-related afferents and topographic connectivity to the thalamus. Hoxa2 inactivation further results in the absence of whisker-related maps in the postnatal brain. Thus, Hoxa2- and rhombomere 3-dependent cues determine the whisker area map and are required for the assembly of the whisker-to-barrel somatosensory circuit.
Assuntos
Proteínas de Homeodomínio/fisiologia , Rombencéfalo/embriologia , Córtex Somatossensorial/anatomia & histologia , Nervo Trigêmeo/embriologia , Vibrissas/inervação , Vias Aferentes , Animais , Axônios/ultraestrutura , Face/inervação , Proteínas de Homeodomínio/genética , Lábio/inervação , Mandíbula/embriologia , Mandíbula/inervação , Camundongos , Camundongos Transgênicos , Mutação , Neurônios Aferentes/citologia , Receptor EphA4/metabolismo , Receptor EphA7/metabolismo , Rombencéfalo/citologia , Rombencéfalo/metabolismo , Córtex Somatossensorial/embriologia , Tálamo/embriologia , Tálamo/metabolismo , Gânglio Trigeminal/embriologia , Gânglio Trigeminal/metabolismo , Nervo Trigêmeo/fisiologia , Núcleos Ventrais do Tálamo/embriologiaRESUMO
Neuronal 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.