Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single brain cells reveal genes controlling formation, development

18.03.2016

In one of the first studies to 'read' the genetic activity inside individual brain cells, University of Wisconsin-Madison neuroscientist Xinyu Zhao has identified the genetic machinery that causes maturation in a young nerve cell. The cells under study came from the hippocampus, a memory-related structure that is the only place in a mammal's brain where new neurons can form throughout life.

Since newly formed neurons were discovered in the hippocampus more than 20 years ago, scientists have identified the many roles they play in learning and memory. However, mystery continues to surround the genetic controls that regulate the formation of the delicate structures and the chemicals necessary for neural communication, Zhao says.


In a new study of mice, neuroscience professor Xinyu Zhao of University of Wisconsin-Madison identifies genetic activity in the adult hippocampus that causes stem cells to mature into fully formed neurons. Green: neural stem cells, some differentiating into neurons. Red: immature neurons.

Credit: Yu Gao, Waisman Center, University of Wisconsin-Madison

In the 1990s, Zhao worked as a postdoctoral fellow with Fred Gage at the Salk Institute for Biological Studies in California, site of groundbreaking discoveries on the formation of new neurons in the hippocampus. Until the discovery of this "adult neurogenesis," scientists thought that the brain essentially had to make do with the supply of neurons it acquired at birth.

The limited supply of new neurons that grows in the hippocampus throughout the lifespan has a role in memory, and perhaps in recovery from degenerative disease.

Zhao, now a professor of neuroscience at UW-Madison, has been probing the adult neurogenesis puzzle for most of her scientific career. "While trying to understand the mechanism that regulates adult neurogenesis, I am also using adult neurogenesis as a model to study brain development and developmental diseases," she says. "In lab animals, adult neurogenesis provides a source of cells that can show us how a neural stem cell develops into a fully-formed neuron."

As might be expected for an organ as fantastically complex as the brain, "neurons come in many varieties," Zhao says, "and their genetic activity changes as they mature. To really understand this process, we need to know which genes are active, and when."

Under study, a group of neurons might average out, which would mask key distinctions at different stages. "When you look at individual cells you can see a lot more information than you can in groups," Zhao says.

Imagine describing the monarch butterfly. Observing the larval stage, you would conclude it's a caterpillar. Watching the insect stage, you would call it a butterfly. But what would you conclude from looking at a mix of caterpillars and butterflies?

The situation in developing neurons is even more confusing, Zhao says. "There are so many different types of neurons, and the stage of development is also critical for understanding the development process."

The technology to leap this hurdle, which can isolate individual neurons so their genes can be extracted, was first used on neurons in 2014.

Taking young neurons from the hippocampus of adult mice, postdoctoral fellows Yu Gao and Feifei Wang (now a member of the faculty at Fudan University in Shanghai) isolated 84 single neurons that had differentiated from neural stem cells at least three days before -- meaning they had started, but not completed, the transformation to a mature neuron.

Once the data on gene activation was assembled, Brian Eisinger, another postdoctoral fellow with expertise in bioinformatics, performed intensive analysis on the rising and falling activity of thousands of genes.

The gene activation profiles of individual cells revealed that the developing neurons go through four stages. But the results also revealed hints about the origin of common neurological conditions.

First, the most active genes during the stem cell phase overlapped significantly with genes implicated in Alzheimer's and Parkinson's diseases. "It surprised us to see that genes associated with the stem cell life stage are highly represented in these neurodegenerative diseases," says Zhao. "We do not know the significance, but it's possible that these conditions are more related to stem cell impairment than we thought."

Second, the gene exhibiting increased activity during neuron maturation overlapped with genes associated with autism. That picture is complex, Zhao acknowledges, as thousands of genes are affected in some way in autism.

"This was an exploratory analysis that may open a new window on understanding complex disorders like autism," Zhao says. "Imagine if you unexpectedly saw a mountain lion's paw print in the forest. Now you would wonder if the lion explained a sudden shortfall of deer in the forest, but you would not know until you looked further."

Junior biochemistry student Laurel Kelnhofer and graduate student Emily Jobe also contributed to the study, published today in the journal Cerebral Cortex.

Although papers using single-cell analysis of mammalian neurons have begun to appear in the last year, they focused on large populations of neurons, Zhao says. "Ours is the first single-cell analysis in adult-born new neurons. Our challenge was that these are scarce, so we had to work hard to optimize our cell isolation procedure."

The study could only be performed at a world-class research institution like UW-Madison, Zhao added. "The Comprehensive Cancer Center provided the cell sorter we needed to get started. The Waisman Center, where I study mechanisms of brain development, had state-of-the-art confocal microscopes and an early model of the single-cell analyzer. The Biotechnology Center has the latest instruments for RNA quantification and ultra-fast RNA sequencing. To advance science, we needed all of these instruments -- and the scientists who know how to run them."

###

The research was funded by the National Institutes of Health, the Waisman Center, the Wisconsin Alumni Research Foundation and the Vilas Trust.

David Tenenbaum
608-265-8549
djtenenb@wisc.edu

Media Contact

Xinyu Zhao
xinyu.zhao@wisc.edu
608-263-9906

 @UWMadScience

http://www.wisc.edu

Xinyu Zhao | EurekAlert!

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Complete skin regeneration system of fish unraveled

24.04.2018 | Life Sciences

Scientists create innovative new 'green' concrete using graphene

24.04.2018 | Materials Sciences

BAM@Hannover Messe: innovative 3D printing method for space flight

24.04.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>