Featured Research

from universities, journals, and other organizations

Protein hub necessary for proper brain development pinpointed: Surprises researchers

Date:
July 29, 2014
Source:
University of North Carolina School of Medicine
Summary:
Researchers have found that the protein glycogen synthase kinase-3, or GSK-3, is crucial for proper brain development early in life, a surprising finding considering that drug companies are searching for ways to limit the protein's function to treat conditions such as bipolar disorder, schizophrenia, and Alzheimer's disease.

Researchers at the UNC School of Medicine have found that the protein glycogen synthase kinase-3, or GSK-3, is crucial for proper brain development early in life, a surprising finding considering that drug companies are searching for ways to limit the protein's function to treat conditions such as bipolar disorder, schizophrenia, and Alzheimer's disease.

Related Articles


The discovery, published today in the journal eLife, also has implications for the study of neurodevelopmental disorders, which can result from abnormal brain formation during embryonic stages and infancy.

"We found that deleting GSK-3 from a specific type of neuron disrupts how those neurons migrate through the cortex," said Meghan Morgan-Smith, PhD, a recent UNC graduate and first author of the eLife paper. Neuron migration is key to how the cerebral cortex becomes organized so it can function properly in adulthood. "The finding was shocking. We thought that deleting GSK-3 would enhance the migration of the neurons. Instead, the opposite happened."

Until now, scientists have viewed GSK-3 as an important drug target because it regulates the function of about 200 other proteins in different kinds of brain cells. In certain conditions, such as schizophrenia and Alzheimer's disease, GSK-3 is thought to inhibit these proteins to a greater degree than is normal. By targeting GSK-3, pharmacologists try to suppress GSK-3's activity so that some of the downstream proteins are released and provide therapeutic effects. This is how, for instance, scientists think lithium works on GSK-3 to treat bipolar disorder.

William Snider, MD, director of the UNC Neuroscience Center and senior author of the eLife paper, said, "Our study shows that we need to be careful when inhibiting GSK-3 because the brain requires its activity for certain developmental and physiological processes."

Snider and Morgan-Smith said that several other proteins had been previously implicated in brain layer formation, but GSK-3 could wind up being the most important regulator of the entire process because it's a hub of cell signaling for so many other proteins.

"We think this finding is the tip of the iceberg in terms of what GSK-3 does to neurons," Snider said. "It likely affects the regulation of where axons extend and what synapses do to brain plasticity, which are critical for normal brain development."

In the embryonic human brain, neurons are born from progenitor cells and then migrate to the outer reaches of the cortex. As new neurons are born, they migrate past the previously-born neurons to their final position. The last neurons born -- cells called layer 2/3 excitatory pyramidal neurons -- migrate past all other neurons to form a new layer just under the skull. In this fashion, neurons form cortical layers that are responsible for higher brain functions, such as learning and memory.

During this layering process, the neurons form axons -- long, arm-like extensions that connect to other cells in the cortex and elsewhere in the brain. When cortical layering goes awry, these axon connections don't form properly. The result can lead to a range of neurodevelopmental disorders, such as intellectual disabilities.

This same layering process occurs in mice, which also have layer 2/3 excitatory pyramidal neurons with GSK-3.

Using mouse genetics and a technique called in utero electroporation, Morgan-Smith was able to delete the GSK-3 gene from just the layer 2/3 excitatory pyramidal neurons and then study what happens to these cells during brain development.

"Deleting GSK-3 completely shut down the system," said Morgan-Smith, who conducted the research while a graduate student in Snider's lab. "The outer cortical layers aren't formed at all. The neurons are scattered throughout the cortex."

Morgan-Smith's research is the first to study the role of GSK-3 in layer 2/3 excitatory pyramidal neurons in a living system. Other studies of GSK-3 were done in cell cultures. Her work took 3 years, and the published work is her dissertation. She's now finishing work in Snider's lab to figure out if deleting GSK-3 affects the way neurons signal to each other.

This research was funded by the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. Morgan-Smith, Y. Wu, X. Zhu, J. Pringle, W. D. Snider. GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation. eLife, 2014; 3 (0): e02663 DOI: 10.7554/eLife.02663

Cite This Page:

University of North Carolina School of Medicine. "Protein hub necessary for proper brain development pinpointed: Surprises researchers." ScienceDaily. ScienceDaily, 29 July 2014. <www.sciencedaily.com/releases/2014/07/140729123744.htm>.
University of North Carolina School of Medicine. (2014, July 29). Protein hub necessary for proper brain development pinpointed: Surprises researchers. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2014/07/140729123744.htm
University of North Carolina School of Medicine. "Protein hub necessary for proper brain development pinpointed: Surprises researchers." ScienceDaily. www.sciencedaily.com/releases/2014/07/140729123744.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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