Featured Research

from universities, journals, and other organizations

Novel analysis sheds new light on the mechanisms of brain development

Date:
August 1, 2011
Source:
Allen Institute for Brain Science
Summary:
Scientists have taken an important step in identifying how the brain organizes itself during development. The findings 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.

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 on August 1, 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 August 1 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.


Story Source:

The above story is based on materials provided by Allen Institute for Brain Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Maureen P. Boyle, Amy Bernard, Carol L. Thompson, Lydia Ng, Andrew Boe, Marty Mortrud, Michael J. Hawrylycz, Allan R. Jones, Robert F. Hevner, Ed S. Lein. Cell-type-specific consequences of reelin deficiency in the mouse neocortex, hippocampus, and amygdala. The Journal of Comparative Neurology, 2011; 519 (11): 2061 DOI: 10.1002/cne.22655

Cite This Page:

Allen Institute for Brain Science. "Novel analysis sheds new light on the mechanisms of brain development." ScienceDaily. ScienceDaily, 1 August 2011. <www.sciencedaily.com/releases/2011/08/110801132533.htm>.
Allen Institute for Brain Science. (2011, August 1). Novel analysis sheds new light on the mechanisms of brain development. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2011/08/110801132533.htm
Allen Institute for Brain Science. "Novel analysis sheds new light on the mechanisms of brain development." ScienceDaily. www.sciencedaily.com/releases/2011/08/110801132533.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins