Role of cell adhesion of neuroepithelium in the developing mouse cerebral cortex *
The cerebral cortex of mammals is a structure consisting of six layers. The progression of layer formation is known to be particularly active during the embryonic and immediate postnatal periods. In the ventricular zones, which adjoin the embryonic cerebral ventricles, neural stem cells differentiate first into neuronal precursor cells and then into neurons. The neurons then migrate toward the surface layer of the brain, forming the 6-layered structure (inside-out). The ventricular zones are thus thought to play an important role in the formation of the brain during the embryonic period. We therefore examined how altering the tissue structure of the cerebral ventricular zones results in abnormalities of the brain formation system. Because the ventricular zones consist of epithelial tissue, the cell junctions are rigid. Consequently, we observed the effect on brain formation of disrupting cell junctions on the ventricular surface, focusing on cadherins, which are calcium (Ca2+)-dependent adhesion molecules between epithelial cells. The experimental method involved injecting ethylene glycol tetraacetic acid (EGTA), which specifically chelates Ca²+, into the cerebral ventricles of 14.5-day-old mouse embryos, then analyzing the tissue structure of the brain in the embryonic and postnatal periods in detail. The results showed that EGTA at high concentration resulted in cerebral edema in some mice. Enlargement of the cerebral ventricles and thinning of the cerebral cortex were also observed. In addition, analysis using SATB2 as a marker of layers 2 and 3 and Ctip2 as a marker of layer 5 showed that although subsequent neurogenesis decreased with the breakdown of the adhesive structure of the ventricular zones, the insideout rule was maintained for the layer structure. These findings show that the ventricular zone structure and neurogenesis in the ventricular zones are unlikely to play a role in the mechanism underlying the inside-out principle. (Accepted on July 23, 2013)
