Featured Research

from universities, journals, and other organizations

A Big Surprise: Young Nerve Cells Can Rewind Their Developmental Clocks

Date:
January 2, 2004
Source:
New York University Medical Center And School Of Medicine
Summary:
Scientists have identified a gene in the cerebral cortex that apparently controls the developmental clock of embryonic nerve cells, a finding that could open another door to tissue replacement therapy in the central nervous system.

Scientists have identified a gene in the cerebral cortex that apparently controls the developmental clock of embryonic nerve cells, a finding that could open another door to tissue replacement therapy in the central nervous system. In a new study, the researchers found that they could rewind the clock in young cortical cells in mice by eliminating a gene called Foxg1. The finding could potentially form the basis of a new method to push progenitor cells in the brain to generate a far wider array of tissue than is now possible.

Related Articles


The study, led by researchers at NYU School of Medicine, is published in the January 2, 2004 issue of Science magazine.

"What we found was a complete surprise," says Gordon Fishell, Ph.D., Associate Professor in the Department of Cell Biology at New York University School of Medicine. "No one had believed that it was possible to push back the birth date of a cortical neuron. There is this central tenet governing the process of brain development, which says that late progenitor cells [forerunners of mature cell types] cannot give rise to cell types produced earlier in development," he explains.

"Consequently, while some populations of stem cells exist in the adult brain, these cells are restricted to producing only a subset of cell types," notes Dr. Fishell. "If one's goal is to produce cells for replacement therapy, some method must be found to turn back the clock and allow adult stem cells to give rise to the wide variety of cells made during normal brain development."

Eseng Lai, Ph.D., of Merck & Co. and one of the study's co-authors, cloned the Foxg1 gene while he was working at Memorial Sloan-Kettering Cancer Center in New York. He also did seminal work in the late 1990s showing that when the gene is eliminated in embryonic mice, the brain's cerebral hemispheres barely develop. Subsequent work demonstrated that the gene played a role in the early phases of cortical development.

The cerebral cortex is massively folded gray matter incorporating billions of neurons. Despite its complexity, the cortex comprises six orderly layers of cortical cells that are laid down during development at a precise time and in a precise sequence. In the study, the researchers asked which cortical cell types embryonic mice lacking Foxg1 can generate. Carina Hanashima, Ph.D., a postdoctoral fellow in Dr. Fishell's laboratory who had previously worked with Dr. Lai, conducted a series of experiments that made the analysis possible.

The progenitor cells for the cortex are born in a zone deep in the brain, and migrate to their assigned layer, depending on the time they are born. So a cortical cell's identity is based on the date of its birth. The first cortical cells to be born populate layer 1, the most superficial layer, which is made up of special Cajal-Retzius (CR) cells. The next cells born migrate to the innermost layer, layer 6. Subsequent layers pile up above layer 6 (between layers 6 and 1), and in descending numerical order from 5 to 2. Each layer has a specific type of neuron associated with it.

The researchers looked at the cortical layers in embryonic mice at a time in their development when layers 1, 6, and 5, would normally have already been formed. In mice lacking the Foxg1 gene, the researchers found that only layer 1, which is made up of CR cells, was present, and these cells were abundant. The absence of other cell types implicated the gene in producing later-born cortical cell types.

One of the ways the scientists were able to identify CR cells was by the expression of a protein called reelin, which plays a vital role in building the developing brain and is only present in CR cells. Mice lacking the protein stumble around so much that they were named "reelers." The cortical layers in these mice are scrambled. In recent years, reelin deficiencies have been linked to such human disorders as schizophrenia and epilepsy.

In subsequent experiments, the researchers asked how the overproduction of CR cells occurs. They used a clever biochemical manipulation that served as a kind of genetic stop watch, allowing them to temporarily turn off the Foxg1 gene in late progenitor cells, after the normal birth date of CR cells had passed. In this way, they observed that cortical cells destined to become layer 5 became CR cells instead. Apparently, the gene orchestrates the program responsible for ensuring that the cortical layers of the cerebral cortex are laid down in a precise sequence. When the gene is inactivated or turned off, the program seems to revert to its earliest stage.

The researchers do not know how late in the game they can play their genetic tricks. If they turn off the Foxg1 gene at a later time in development, such as when cortical layers 2 or 3 are forming, will progenitor neuronal cells still become CR cells? Are there other genes that control the developmental clock? If such genes exist, it may be possible to turn these genes off in adult neural stem cells, and thereby generate a far broader array of tissue than otherwise possible. "I would say that the chances of this happening are very remote," says Dr. Fishell, "but then again, I never thought that the clock could have been turned back in neuronal progenitor cells."

The authors of the study are Gordon Fishell and Carina Hanashima of NYU School of Medicine; Eseng Lai of Merck; Suzanne Li of Memorial Sloan-Kettering Cancer Center; and Lijian Shen of Weill Medical College of Cornell University.


Story Source:

The above story is based on materials provided by New York University Medical Center And School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

New York University Medical Center And School Of Medicine. "A Big Surprise: Young Nerve Cells Can Rewind Their Developmental Clocks." ScienceDaily. ScienceDaily, 2 January 2004. <www.sciencedaily.com/releases/2004/01/040102071103.htm>.
New York University Medical Center And School Of Medicine. (2004, January 2). A Big Surprise: Young Nerve Cells Can Rewind Their Developmental Clocks. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2004/01/040102071103.htm
New York University Medical Center And School Of Medicine. "A Big Surprise: Young Nerve Cells Can Rewind Their Developmental Clocks." ScienceDaily. www.sciencedaily.com/releases/2004/01/040102071103.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) Video provided by AP
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