Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus

S Horng , C Ellsworth, G Kreiman, and M Sur.

Department of Brain & Cognitive Sciences, The Picower Center for Learning and Memory, MIT, Cambridge, MA, USA

The thalamus serves as the principal relay, as well as processing, station for nearly all incoming sensory information to the cortex. During development, the diencephalon gives rise to dorsal and ventral subdivisions of the thalamus, which further parcellate into functional nuclei within sensory-specific pathways. These nuclei include the lateral geniculate nucleus (LGN) and medial geniculate nucleus (MGN), well-studied targets of visual and auditory afferents, respectively. As in the cortex, the molecular mechanisms of thalamic arealization are not well understood. Experiments in which visual afferents are rerouted to a structurally intact MGN after auditory deafferentation suggest that intrinsic factors maintain the structural integrity of thalamic nuclei, while extrinsic factors potentially modulate functional connectivity. In order to discover candidate molecules for intrinsic thalamic patterning, we used Affymetrix u74v2 microarrays to catalog differential gene expression between the LGN and MGN of mouse neonatal (P0) thalamus. From a screen of 34,600 probe sets, only sixty-four probes showed differential expression levels (p<0.05) and a fold-change >2, corresponding to 22 genes more highly expressed in the LGN, and 19 genes in the MGN. SQ-PCR confirmed the expression data of selected genes and in situ hybridization characterized expression anatomically. We report a group of novel genes, including 4 members of the Zic family of transcription factors, that are significantly enriched in the neonatal LGN. For the first time, we identify a group of MGN-enriched molecules, including the strong histologic markers, Foxp2, Crabp2, and Ssbp2. Finally, using a computational analysis that searches for common cis-regulatory elements among co-expressed genes, we propose a regulatory pathway for functional development within the LGN. This pathway involves two parallel streams regulated by Pax6 and Lhx1 and provides a potential conceptual framework for understanding the differentiation of the dorsal thalamus.

Supported by NIH grant EY014134