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.
Highlights
Thalamic projection to specific areas of the cortex (Cx) is fundamental in the development of conscious sensory and motor functions, and thalamic neurons projecting to the Cx present homogeneous morphology (Jones 2007; Clascá et al 2012)
90 genes were identified with expression in the thalamic mantle layer (TML) at E13.514.5, but only 12 genes showed clear regional expression: BC055811, BC062109, BTB (POZ) domain containing 3 (Btbd3), EG628779, Elmo1, Igsf2, Phosphodiesterase 10A (Pde10a), Rapgef3, Slc6a7, Slitrk6, Srgap2 and Trim9
The presence of normal radial glia cells and fibers in F gf8null/ neo mice at these stages were detected through anti-GFAP and vimentin immunohistochemistry. These results suggest that Fibroblast growth factor 8 (Fgf8) morphogenetic activity in the ventricular epithelium is translated to the TML by the expression of pERK in radial glia fibers, which seems to be required for cell survival and appropriate nuclear patterning
Summary
Thalamic projection to specific areas of the cortex (Cx) is fundamental in the development of conscious sensory and motor functions, and thalamic neurons projecting to the Cx present homogeneous morphology (Jones 2007; Clascá et al 2012). The organized pattern of TC is a consequence of elaborate mechanisms of positional information in thalamic neurons and axonal navigation (Garel and López-Bendito 2014). The expressions of Netrin (Ntn1), Slit 1, Robo, Sema3A and EphrinA5 in the ventral telencephalon (VTel) act as molecular signals for thalamic axon navigation, to innervate the Cx (Andrews 2006; Bagri et al 2002; Bielle et al 2011; Bonnin et al 2007; Braisted et al 2000; López-Bendito et al 2006; Serafini et al 1996). Axons grow from the thalamus (Th) to prethalamus (PTh), entering the internal capsule between embryonic days 12–15 (E12 to E15), reaching the cortical subplate (SP) at E14-16, and invading Cx by E18 (Ghosh et al 1990; Squarzoni 2015)
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