The ‘neuronal big bang’ is visualised for the first time.


The human brain is home to many different types of neurons with their own genetic signature to define 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.  However, the action by which neuronal identity is dynamically specified upon progenitor division is unknown.  Now, researchers at the University of Geneva (UNIGE) have developed a novel technology called FlashTag that enables them to isolate and visualize neurons at the very moment they are born.  The team state that they have deciphered the basic genetic code allowing the construction of a neuron which will allow the global medical community to understand how the human brain develops and how to use this code to reconstruct neurons from stem cells.  The study is published in the journal Science.

Previous studies show that neurogenesis is the process by which neurons are generated from neural stem cells and progenitor cells.  Neurogenesis, the birth of neurons, is most active during pre-natal development and is responsible for populating the growing brain with neurons. In mammals, adult neurogenesis has been shown to occur in multiple brain structures, including the dentate gyrus of the hippocampus and the olfactory bulb.  However, researchers only had a few photos to reconstruct the history of neurons, which left a lot of room for speculation.  The current study developed a technology termed FlashTag, which visualizes neurons as they are being born.

The current study utilised FlashTag to tag progenitors with a fluorescent marker at the very moment it divides, the tag also persists in its progeny. Results show that newborn neurons can be visualized and isolated in order to dynamically observe which genes are expressed in the first few hours of their existence. Data findings show that over time, the newborn neurons can then be studied for their evolution and changes in gene expression.

The lab state that due to FlashTag, there is now a full genetic movie available.  They go on to add that every instant becomes visible from the very beginning, which allows them to understand the developmental scenario at play, identify the main characters, their interactions and their incentives. Working in the cerebral cortex of the mouse, the group identified the key genes responsible for neuronal development, and demonstrated that their expression dynamics is essential for the brain to develop normally.

Results show that after successfully reading this genetic code, the team were able to rewrite it in newborn neurons. Data findings show that by altering the expression of certain genes, they were able to accelerate neuronal growth, thus altering the developmental script. The researchers note that 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.  They go on to add that researchers will now be able to better understand the mechanisms underlying neurological diseases such as autism and schizophrenia.

The team surmise that by giving access to the primordial code of the formation of neurons they have raised the  understanding for how neurons function in the adult brain. They go on to add that it also appears that several of these original genes are also involved in neurodevelopmental and neurodegenerative diseases, which can occur many years later. For the future, the researchers state that this suggests a predisposition may be present from the very first moments in existence for neurons, and that environmental factors can then impact on how diseases may develop later on. They go on to conclude that by understanding the genetic choreography of neurons, the global community can observe how these genes behave from inception, and identify potential anomalies predicting diseases.

Source: University of Geneva (UNIGE)

 

Neural Progenitor cells.  Credit: Prof Chandran lab.

Neural Progenitor cells. Credit: Prof Chandran lab.

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