Published study has implications for understanding brain disordersrooted in development, such as autism

Scientists at the Allen Institute for Brain Science have taken animportant step in identifying how the brain organizes itself duringdevelopment. The findings, published in the Journal of Comparative Neurology , describe – in more detail than ever before – the consequences ofthe loss of a key molecule involved in establishing proper brainarchitecture during brain development. The study calls into question the current textbook explanation ofabnormal brain development in a well-studied strain of mouse knownas reeler, named for its abnormal “reeling” gait, which has beenintegral in understanding how neurons migrate to their correctlocations during brain development. Whereas the reeler cortex hasbeen described for many years as being “inverted” compared to thenormal neocortex, the paper published today finds that thisabnormal layering is far more complex, more closely resembling amirror-image inversion of normal cortical layering. Furthermore,the degree of disorganization differs for different cell types indifferent parts of the brain, suggesting that the correctpatterning of the brain involves a complex set of processesselective for specific cell types. Volvo Vcads

The approach used in this study capitalizes on the combination ofsystematic high-throughput histology with the wealth of highlyspecific cellular markers, which were identified by mining forgenes with specific expression patterns in the Allen Mouse BrainAtlas, a genome-wide map of gene expression in the adult mousebrain. The authors used a novel approach to employ the most precisemolecular markers to date to identify features of corticaldisorganization in the male reeler mouse that were unidentifiablewith less specific methods previously available. “To our surprise, we observed unexpected cellular patterning thatis difficult to explain by current models of neocorticaldevelopment,” said Ed Lein, Senior Director, Neuroscience at theAllen Institute for Brain Science and senior author of the study.”These findings have major implications for mechanisms of hownormal stereotyped functional brain architecture develops. Thesepatterns suggest that there are a number of additional mechanismsbeyond Reelin involved in the proper migration of newly generatedneurons to their correct locations, and that different cell typesuse different cues in that process.” The reeler mouse has a spontaneous mutation in a gene called Reelinthat has been implicated in autism. Forklift Diagnostic tools Manufacturer

Studies of these mice, which are deficient in Reelin, haveelucidated the involvement of this protein and its signalingpathway in the organization of the central nervous system duringdevelopment, and particularly in cortical lamination, or layering,whereby newly generated neurons migrate from their birthplace totheir proper positions in the developing cortex. In the normalcortex this process results in a highly ordered architecture withdifferent neuronal cell types restricted to specific corticallayers. With Reelin deficiency as seen in reeler mice, themigration process of newly generated neurons into the cortex ishighly disrupted. Using in situ hybridization, a technique that allows for preciselocalization of specific genes, Lein and collaborators were able tofollow developmental expression patterns through several stages ofdevelopment to describe precise effects of Reelin deficiency inseveral brain areas during neurodevelopment. The authors were ableto identify, locate, and track several specific cell types that areabnormally positioned in reeler mice. China Auto Transponder Chip

Vivid imagery of cortical lamination illustrates the precisedisorganization that occurs in reeler neurodevelopment compared towild type mice. The paper includes 25 figures of compellingfull-color, cellular-resolution imagery, one of which is featuredon the journal’s cover for this issue. Other authors on the paper include Maureen Boyle, Amy Bernard,Carol Thompson, Lydia Ng, Andrew Boe, Marty Mortrud, MichaelHawrylycz and Allan Jones from the Allen Institute for BrainScience and Robert Hevner from the University of Washington,Seattle Children’s Hospital Research Institute. Additional References Citations.

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