Scientists pinpoint what makes brain cells develop in a specific order
A study of the visual system of fruit flies reveals factors regulating
neuron development and uncovers similarities with human brain development

Date:
April 6, 2022
Source:
New York University
Summary:
Researchers have identified the complete series of 10 factors
that regulate the development of brain cell types in the visual
system of fruit flies -- including in what order these neurons
develop. The findings open new avenues of research to understand
how brain development evolved in different animals and hold clues
for regenerative medicine.



FULL STORY ========================================================================== Researchers have identified the complete series of 10 factors that
regulate the development of brain cell types in the visual system of fruit flies - - including in what order these neurons develop. The findings, published in Nature, open new avenues of research to understand how brain development evolved in different animals and hold clues for regenerative medicine.


==========================================================================
The human brain is composed of 80 billion neurons. These nerve cells
differ in their form, function, and connectivity with other neurons to
form neural networks. This complexity allows the brain to perform its
many functions, from controlling speech and vision to storing memories
and generating emotions.

While scientists have identified many types of neurons, how this
complexity arises during the brain's development is a central question
for developmental neurobiology and regenerative medicine.

"Knowing how the human brain develops could allow us in the future to
repeat these developmental processes in the lab to generate specific
types of neurons in a Petri dish -- and potentially transplant them
in patients -- or to trigger neuronal stem cells in living organisms
to generate and replace missing neurons," said Claude Desplan, Silver
Professor of Biology at NYU and the study's senior author.

Because studying the human brain is an incredibly complex endeavor,
researchers rely on model organisms, such as mice and flies, to explore
the intricate mechanisms involved in the brain's processes. In both vertebrates, like mice and humans, and invertebrates, like flies,
different types of neurons are generated sequentially as the brain
develops, with specific types of neurons being generated first and other
types being generated later from the same progenitor stem cell.

The mechanism by which neural stem cells produce different neurons over
time is called temporal patterning. By expressing different molecules
-- termed temporal transcription factors, or tTFs -- that regulate the expression of specific genes in each window of time, neural stem cells
produce different neurons.



==========================================================================
In the research published in Nature, the researchers studied the brains
of the fruit fly Drosophila to uncover the complete set of tTFs needed to generate the roughly 120 neuron types of the medulla, a specific brain structure in the visual system of flies. They used state-of-the-art
single-cell mRNA sequencing to obtain the transcriptome -- all of
the genes expressed in a given cell -- of more than 50,000 individual
cells that were then grouped into most of the cell types present in the developing medulla.

Focusing on neural stem cells, the researchers identified the complete
set of tTFs that define the different windows of time in this brain
region and the genetic network that controls the expression of these
different tTFs that allow this temporal cascade to progress.

"Several tTFs had been previously identified in the brain's visual system
using available antibodies; we have now identified the comprehensive
series of 10 tTFs that can specify all the neuron types in this brain
region," said one of the study's lead authors, Nikolaos Konstantinides,
now a group leader at the Institut Jacques Monod in Paris and a former postdoctoral fellow in the Desplan lab.

The researchers then identified the genetic interactions that allow the temporal cascade to progress and how this progression relates to the
"birth order" of all neurons in the medulla, linking specific temporal
windows with the generation of specific types of neurons. This cascade
is necessary to produce the full extent of neural diversity of this
brain region in a stereotypic order.

"Impairment of the temporal cascade progression leads to the generation
of reduced neuronal diversity, hence altering brain development," said
Isabel Holguera, a postdoctoral fellow in NYU's Department of Biology
and one of the study's co-first authors.

Finally, the team examined the first steps in the process of neural
stem cells maturing into neurons, a stage in neuron development called differentiation.

They found that the differentiation process for fly neurons and human
cortical neurons was remarkably alike, with similar patterns of genes
expressed during the various stages of differentiation.

"Our findings suggest that understanding the mechanisms of neuron
development in flies can generate insight for the equivalent process in humans," said co- first author Anthony Rossi, now a postdoctoral fellow
at Harvard and a former graduate student in the Desplan lab.

Additional study authors include Aristides Escobar, Lie'baut Dudragne,
Yen- Chung Chen, Thinh Tran, Azalia Martinez Jaimes, Mehmet Neset
O"zel, and Fe'lix Simon of NYU; Zhiping Shao, Nadejda M. Tsankova,
John F. Fullard, and Panos Roussos of the Icahn School of Medicine at
Mount Sinai; and Uwe Walldorf of Saarland University. The research was supported by the National Institutes of Health (EY019716, EY10312, K99 EY029356-01, T32 HD007520), NYU, the Human Frontier Science Program,
and the Leon Levy Foundation.


========================================================================== Story Source: Materials provided by New_York_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Nikolaos Konstantinides, Isabel Holguera, Anthony M. Rossi,
Aristides
Escobar, Lie'baut Dudragne, Yen-Chung Chen, Thinh N. Tran, Azalia M.

Marti'nez Jaimes, Mehmet Neset O"zel, Fe'lix Simon, Zhiping Shao,
Nadejda M. Tsankova, John F. Fullard, Uwe Walldorf, Panos Roussos,
Claude Desplan. A complete temporal transcription factor series in
the fly visual system. Nature, 2022; DOI: 10.1038/s41586-022-04564-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220406132416.htm

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