Molecular Mechanism of Cortical Area Specification

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1. The mammalian neocortex develops layer organizations with regional differences represented by expression of multiple genes at embryonic stages. These genes could play important roles in the formation of areal cyto-architecture, yet, the number of genes identified so far is not sufficient to explain such intricate processes. Here we collected five regions-the medial, dorsal, lateral, rostral and occipital from the dissected E 16.5 mouse cerebral cortex, performed extensive gene expression analysis using DNA microarray, and reached the successful identification of seven genes from the dorsal region, three genes from the medial region, and three genes from the lateral region. Particularly, all seven genes identified in the dorsal region demarcated the future somatosensory and auditory areas in the cortical plate with high rostrolateral-low caudomedial gradation. Furthermore, the regional expression pattern of NeuropeptideY was shifted rostral and the layer specificity was disorganized … More in the Pax6-deficient mice. Our results provide new information about a subclass of regionally expressed genes in the cortical plate at the late embryonic stage, which may help understand the molecular mechanisms of neocortical arealization.2. Next, we challenged the somatosensory patterning mechanism by investigating the role of a peripheral whisker pattern for the patterning of the mouse somatosensory trigeminal projection at the brainstem and thalamus. The whisker pattern was manipulated by infecting the embryonic epidermis with adenovirus harboring Shh. The ectopic expression of Shh led to the induction of extra whiskers and displacement of whiskers, where these whiskers were histologically normal. The altered whisker pattern was isomorphically represented in the brainstem (barrelette: subnuclei principalis and subnuclei interpolaris), thalamus (barreloid) and cortex (barrel). These results highlight the role of the peripheral whisker pattern for the central patterning of the brainstem, thalamus, and cortex in the mouse somatosensory system.3. Finally, we examined the thalamocortical and corticofugal pathway in developing Fezl-deficient mice (Dr. Masahiko Hibi at Riken). The fez-like (Fezl) protein is a transcriptional repressor selectively expressed in the deep layers of the developing cortex. In normal mice, cortical and thalamic axons meet in the internal capsule between embryonic day (E) 13.5 and E14.5 and fasciculate with each other as they extend to their targets, namely, the thalamus and cortex, respectively. In Fezl-deficient mice, most of the thalamic and cortical axons stop in the internal capsule and at the pallial-subpallial boundary, respectively, at E14.5. Based upon previous studies, the present study suggests that the aberrant trajectories of the thalamocortical axons in Fezl-deficient mice are caused by defects in the cortical efferent neurons that express Fezl. Less