Scientists at the Allen Institute for Brain Science have taken an important step in identifying how the brain organizes itself during development. The findings, published in the Journal of Comparative Neurology today, describe – in more detail than ever before – the consequences of the loss of a key molecule involved in establishing proper brain architecture during brain development.
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.
"To our surprise, we observed unexpected cellular patterning that is difficult to explain by current models of neocortical development," said Ed Lein, Senior Director, Neuroscience at the Allen Institute for Brain Science and senior author of the study. "These findings have major implications for mechanisms of how normal stereotyped functional brain architecture develops. These patterns suggest that there are a number of additional mechanisms beyond Reelin involved in the proper migration of newly generated neurons to their correct locations, and that different cell types use different cues in that process."
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. In the normal cortex this process results in a highly ordered architecture with different neuronal cell types restricted to specific cortical layers. With Reelin deficiency as seen in reeler mice, the migration process of newly generated neurons into the cortex is highly disrupted.
Using in situ hybridization, a technique that allows for precise localization of specific genes, Lein 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.
Vivid imagery of cortical lamination illustrates the precise disorganization that occurs in reeler neurodevelopment compared to wild type mice. The paper includes 25 figures of compelling full-color, cellular-resolution imagery, one of which is featured on 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, Michael Hawrylycz and Allan Jones from the Allen Institute for Brain Science and Robert Hevner from the University of Washington, Seattle Children's Hospital Research Institute.
Boyle MP, Bernard A, Thompson CL, Ng L, Boe A, et al. (2011) Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala. Journal of Comparative Neurology 519: 2061-89. doi: 10.1002/cne.22655
About the Allen Institute for Brain Science
The Allen Institute for Brain Science (www.alleninstitute.org) is an independent, 501(c)(3) nonprofit medical research organization dedicated to accelerating understanding of the human brain by fueling discovery for the broader scientific community. Through a product-focused approach, the Allen Institute generates innovative public resources used by researchers and organizations around the globe. Additionally, the Institute drives technological and analytical advances, thereby creating new knowledge and providing new ways to address questions about the brain in health and disease. Started with $100 million in seed money from philanthropist Paul G. Allen, the Institute is supported by a diversity of public and private funds. The Allen Institute's data and tools are publicly available online at www.brain-map.org.
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
19.03.2018 | Physics and Astronomy
19.03.2018 | Materials Sciences
19.03.2018 | Event News