Development of Thalamocortical Projections in Normal and Mutant Mice

In vitro and in vivo studies have begun to reveal multiple mechanisms involved in the development of thalamocortical projections. Different cellular and molecular interactions dominate during the various stages of axon elongation, target selection, and establishment of layer- and area-specific connections. Recent work points to the crucial role of the early-developing thalamocortical projections and their interactions with the developing cortical circuitry in establishing the functional and structural organization of the cortex. In this chapter we give an overview of mutant mice, including knockout (KO) mice which have homozygous null gene mutations, which are providing interesting paradigms for distinct phases of thalamocortical development. We present selected mutants in two major groups. The first group involves mutations that directly influence some key mechanism of axon elongation and delivery (reeler mutant, L1 KO, TBR-1 KO, Pax-6 KO) or thalamocortical interactions (Adcyl Barrelless, MAO-A KO, NMDA receptor mutant, PLC-β1 KO, GAP-43 KO). The second group (albino, anophthalmic mice, mice with extra vibrissae) includes mutations that do not affect thalamocortical outgrowth or the interactions between thalamic projections and cortical circuitry itself, but instead alter the sensory flow of information from the periphery and influence thalamocortical development. The number of available mutants is increasing rapidly and, combined with recent technology allowing gene expression to be experimentally manipulated in precise spatiotemporal patterns, will provide further understanding of the development and plasticity of thalamocortical connections.