The early topography of thalamocortical projections is shifted inEbf1andDlx1/2mutant mice

Abstract

The prevailing model to explain the formation of topographic projections in the nervous system stipulates that this process is governed by information located within the projecting and targeted structures. In mammals, different thalamic nuclei establish highly ordered projections with specific neocortical domains and the mechanisms controlling the initial topography of these projections remain to be characterized. To address this issue, we examined Ebf1 -/-embryos in which a subset of thalamic axons does not reach the neocortex. We show that the projections that do form between thalamic nuclei and neocortical domains have a shifted topography, in the absence of regionalization defects in the thalamus or neocortex. This shift is first detected inside the basal ganglia, a structure on the path of thalamic axons, and which develops abnormally in Ebf1 -/-embryos. A similar shift in the topography of thalamocortical axons inside the basal ganglia and neocortex was observed in Dlx1/2 -/-embryos, which also have an abnormal basal ganglia development. Furthermore, Dlx1 and Dlx2 are not expressed in the dorsal thalamus or in cortical projections neurons. Thus, our study shows that: (1) different thalamic nuclei do not establish projections independently of each other; (2) a shift in thalamocortical topography can occur in the absence of major regionalization defects in the dorsal thalamus and neocortex; and (3) the basal ganglia may contain decision points for thalamic axons' pathfinding and topographic organization. These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia.

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

“…The functional specialization of each area depends on this input, as does the development of areaspecific functional architecture (Rakic, 1988;Sur et al, 1988;Sur et al, 1990;Rakic et al, 1991;Iwasato et al, 2000;Sharma et al, 2000;Guillery and Sherman, 2002;Kahn and Krubitzer, 2002;Sherman and Guillery, 2002). How thalamocortical innervation is set up in development remains a focus of concentrated investigation (Garel et al, 2002;Hevner et al, 2002;Lopez-Bendito et al, 2002;Dufour et al, 2003;Seibt et al, 2003;Garel and Rubenstein, 2004).…”

Diffusion and imaging properties of three new lipophilic tracers, NeuroVue™ Maroon, NeuroVue™ Red and NeuroVue™ Green and their use for double and triple labeling of neuronal profile

“…Several blue-excited lipophilic dyes exist (DiA, DiO; [12,13,27]; www.probes.com) that allow double labeling, albeit with variable degrees of difficulty and/or success. Some researchers reported that these dyes allowed them to image partial segregation of two labeled neuronal profiles [18], while others reported several problems that were incompletely resolved or not resolvable using DiI in combination with DiA or DiO.…”

Thalamocortical Pathfinding Defects Precede Degeneration of the Reticular Thalamic Nucleus in Polysialic Acid-Deficient Mice

“…This process of selective fasciculation and contact guidance has been proposed to be required for the highly organized entry of thalamocortical fibers into the cortical plate as well as for corticothalamic fibers to be guided toward their targets (Molnár, 2000;Molnár et al, 2003). Other experimental data, however, suggest that the reciprocal connections between thalamus and cortex can develop independently of each other (Garel et al, 2002;Torii and Levitt, 2005). In II Ϫ/Ϫ IV Ϫ/Ϫ mice, the misguidance of thalamocortical fibers prevents the encounter of thalamocortical and corticofugal fibers and no entry of NFpositive corticothalamic projections into the internal capsule was observed at E14.5 and P1.…”