Radial glia fibers translate Fgf8 morphogenetic signals to generate a thalamic nuclear complex protomap in the mantle layer

Abstract

Thalamic neurons are distributed between different nuclear groups of the thalamic multinuclear complex; they develop topologically ordered specific projections that convey information on voluntary motor programs and sensory modalities to functional areas in the cerebral cortex. Since thalamic neurons present a homogeneous morphology, their functional specificity is derived from their afferent and efferent connectivity. Adequate development of thalamic afferent and efferent connections depends on guide signals that bind receptors in nuclear neuropils and axonal growth cones, respectively. These are finally regulated by regionalization processes in the thalamic neurons, codifying topological information. In this work, we studied the role of Fgf8 morphogenetic signaling in establishing the molecular thalamic protomap, which was revealed by Igsf21, Pde10a and Btbd3 gene expression in the thalamic mantle layer. Fgf8 signaling activity was evidenced by pERK expression in radial glia cells and fibers, which may represent a scaffold that translates neuroepithelial positional information to the mantle layer. In this work, we describe the fact that Fgf8-hypomorphic mice did not express pERK in radial glia cells and fibers and presented disorganized thalamic regionalization, increasing neuronal death in the ventro-lateral thalamus and strong disruption of thalamocortical projections. In conclusion, Fgf8 encodes the positional information required for thalamic nuclear regionalization and the development of thalamocortical projections.