http://www.alphagalileo.org/ViewItem.aspx?ItemId=161704&CultureCode=en
Our brain is home to different types of
neurons, each with their own genetic signature that defines their
function. These neurons are derived from progenitor cells, which are
specialized stem cells that have the ability to divide to give rise to
neurons. Today, neuroscientists from the Faculty of Medicine at the
University of Geneva (UNIGE) shed light on the mechanisms that allow
progenitors to generate neurons. By developing a novel technology called
FlashTag that enables them to isolate and visualize neurons at
the very moment they are born, they have deciphered the basic genetic
code allowing the construction of a neuron. This discovery, which is
published today in Science, allows not only to understand how
our brain develops, but also how to use this code to reconstruct neurons
from stem cells. Researchers will now be able to better understand the
mechanisms underlying neurological diseases such as autism and
schizophrenia.
Directed by Denis Jabaudon, a
neuroscientist and neuroscientist at the Department of Basic
Neurosciences at UNIGE Faculty of Medicine and neurologist at the
University Hospitals Geneva (HUG), the researchers developed a
technology termed FlashTag, which visualizes neurons as they
are being born. Using this approach, at the very moment where a
progenitor divides, it is tagged with a fluorescent marker that persists
in its progeny. Scientists can then visualize and isolate newborn
neurons in order to dynamically observe which genes are expressed in the
first few hours of their existence. Over time, they can then study
their evolution and changes in gene expression. «Previously, we only had
a few photos to reconstruct the history of neurons, which left a lot of
room for speculation. Thanks to FlashTag, there is now a full
genetic movie unfolding before our eyes. Every instant becomes visible
from the very beginning, which allows us to understand the developmental
scenario at play, identify the main characters, their interactions and
their incentives», notes Denis Jabaudon. Working in the cerebral cortex
of the mouse, the scientists have thus identified the key genesto
neuronal development, and demonstrated that their expression dynamics is
essential for the brain to develop normally.
A very precise primordial choreography
This discovery, by giving access to the
primordial code of the formation of neurons, helps us to understand how
neurons function in the adult brain. And it appears that several of
these original genes are also involved in neurodevelopmental and
neurodegenerative diseases, which can occur many years later. This
suggests that a predisposition may be present from the very first
moments in the existence of neurons, and that environmental factors can
then impact on how diseases may develop later on. By understanding the
genetic choreography of neurons, the researchers can therefore observe
how these genes behave from the start, and identify potential anomalies
predicting diseases.
After successfully reading this genetic
code, the scientists we able to rewrite it in newborn neurons. By
altering the expression of certain genes, they were able to accelerate
neuronal growth, thus altering the developmental script. With FlashTag,
it is now possible to isolate newborn neurons and recreate cerebral
circuits in vitro, which enables scientists to test their function as
well as to develop new treatments.
A website open to all
The UNIGE team posted a website where it
is possible to enter the name of a gene and observe how it is
expressed, and how it interacts with other genes. «Each research team
can only focus on a handful of genes at a time, while our genome is made
up of close to 20,000 genes. We therefore made our tool available for
other researchers to use it, in a fully open way,» highlights Denis
Jabaudon.
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