The study calls into question the current textbook explanation of abnormal brain development in a well-studied strain of mouse known as reeler, named for its abnormal "reeling" gait, which has been integral in understanding how neurons migrate to their correct locations during brain development. Whereas the reeler cortex has been described for many years as being "inverted" compared to the normal neocortex, the paper published today finds that this abnormal layering is far more complex, more closely resembling a mirror-image inversion of normal cortical layering.
Furthermore, the degree of disorganization differs for different cell types in different parts of the brain, suggesting that the correct patterning of the brain involves a complex set of processes selective for specific cell types.
The approach used in this study capitalizes on the combination of systematic high-throughput histology with the wealth of highly specific cellular markers, which were identified by mining for genes with specific expression patterns in the Allen Mouse Brain Atlas, a genome-wide map of gene expression in the adult mouse brain. The authors used a novel approach to employ the most precise molecular markers to date to identify features of cortical disorganization in the male reeler mouse that were unidentifiable with less specific methods previously available.
The reeler mouse has a spontaneous mutation in a gene called Reelin that has been implicated in autism. Studies of these mice, which are deficient in Reelin, have elucidated the involvement of this protein and its signaling pathway in the organization of the central nervous system during development, and particularly in cortical lamination, or layering, whereby newly generated neurons migrate from their birthplace to their proper positions in the developing cortex.
Using in situ hybridization, a technique that allows for precise localization of specific genes, Ed Lein, Senior Director, Neuroscience at the Allen Institute for Brain Science, and collaborators were able to follow developmental expression patterns through several stages of development to describe precise effects of Reelin deficiency in several brain areas during neurodevelopment. The authors were able to identify, locate, and track several specific cell types that are abnormally positioned in reeler mice.
MEDICA.de; Source: Allen Institute for Brain Science