We are mostly focusing on the cellular and molecular machinery to build up the mammal specific brain structure ‘cerebral cortex’ during development and/or evolution. The cerebral cortex, the higher cognitive center of the mammalian brain, is radially laminated into six layers with the width and/or neuronal-axonal density of each layer varying among the tangential domains (i.e. frontal ⇔ occipital, parietal ⇔ temporal lobes). This has already been reported by Brodmann in 1905 and the following series of analyses have confirmed that such tangential cytoarchitectonic differences in the cerebral cortex well coincide with the functional domains determined by the electrophysiological means of evaluation. These regional units in the cerebral cortex are currently called ‘functional areas’ and it is totally essential for coordinated task of the brain to arrange them into precise positions during development: Arealization defects in the human cerebral cortex indeed result in malfunction of the brain such as epilepsy and psychiatric diseases. Hence, it would extremely be crucial in understating the formidable questions such as the theory of mind and/or mental health to thoroughly address genetic machinery for cortical arealization. Yet, little is known about how functional areal differences in the cerebral cortex emerge during development and/or evolution.
We are currently analyzing how those genes showing areal specificity in the developing mouse cerebral cortex can establish their specific expression patterns during development and may eventually contribute to the cortical arealization dynamics or not. Additionally, by utilizing regulatory regions (i.e. enhancer/promoters) from those genes, we are trying to genetically trace the dynamic cellular processes in mouse cortical arealization. Furthermore, we are planning to study the evolutionary traits of those genes by means of comparative genomics as well as in the context of xeno-transgenesis.
For those purposes, we are developing variety of unique yet powerful methods in the lab, in addition to the standard methodology for cell and molecular biology. For instance, we have fine tools to engineer the stably replicable genome unit from any species, bacterial artificial chromosome (BAC), by means of homologous recombination as well as transposon integration. We also sharpen special techniques for manipulating/culturing mouse embryos, which allow us to effectively deliver any charged molecules such as DNAs (including modified BACs), RNAs and proteins into mouse embryos by means of in vivo electroporation or microinjection. Based on our techniques, we recently improve the CRISPR/Cas9-mediated genome editing method in fertilized mouse eggs for efficient generation of knock-out and knock-in mice. These original methods can be mastered even within the period of graduation research under the kind and careful guidance of our lab specialists, which would be very useful and helpful in the future career development.
We always welcome those who interested in our research or special techniques and are going to occasionally accept postdocs, students and technicians. Please contact us for further information (contact address by e-mail: tinoue[at]ncnp.go.jp; Please replace [at] to @ in sending e-mail to T. Inoue).