The research team
has identified the underlying genetic programs involved in the growth and
differentiation of different types of
and how they connect
with the precise visual areas of the brain that are crucial for the
interpretation of visual signals. Additionally, several new genes have been
discovered that are essential in the regulation of nerve growth, which could
have positive implications in
findings have been published in the journal Development
, which is a
publication of the Company of Biologists, UK.
The study was led
by Dr. Pierre Fabre, Ph.D., who is a Senior Researcher in the Department of Basic
Neurosciences, Faculty of Medicine at the University of Geneva, Switzerland.
The first author
of the paper was Quentin Lo Giudice, who is a Ph.D. student
in the Department of Basic Neurosciences, Faculty of Medicine at the University
of Geneva, Switzerland.
collaborators included Dr. Gioele La Manno, Ph.D., and Dr.
Marion Leleu, Ph.D. Dr. Manno is the Principal Investigator
of the Neurodevelopmental Systems Biology Laboratory at the Brain Mind
Institute, School of Life Sciences at the Swiss Federal Institute of Technology
Lausanne or École Polytechnique Fédérale de Lausanne (EPFL), Lausanne,
Switzerland. Dr. Leleu is a Scientist in the Gene Expression Core Facility at
EPFL, Lausanne, Switzerland.
Composition of the Visual System of Humans
The visual system
of humans is composed of various types of neurons that must accurately connect
with specific areas in the brain in order to generate the sensation of vision.
These precise connections enable the brain to transform signals received from
the eyes into visual images.
There are a variety
of cell types involved in the generation of the sensation of vision. For
example, the photoreceptors present in the retina pick-up light signals, while
the neurons of the optic nerve conduct these signals to the brain. After the
nerve signals reach the brain, the cortical neurons present in the visual
cortex transform these electrical signals into actual visual images.
Additionally, there are interneurons that interconnect various nerve cell types
to form a neural network. All these neurons are derived from progenitor cells
that have the capacity of giving rise to different types of nerve cells, each
having a specialized function.
Gene Sequencing and Mapping of Retinal Cells
In order to
elucidate the underlying genetic mechanism involved in the development and
functioning of the retina, the researchers monitored gene activity by looking
expression patterns of individual retinal cells
. They sequenced more
than 6,000 retinal cells during the development of the retina in order to better
understand the early specification of these retinal neurons. Using the
generated sequencing data, the researchers conducted large-scale bioinformatic
analyses to interpret the findings.
The research team
also studied the behavior of the progenitor cells during the cell cycle as well
as during their progressive differentiation into various other types of cells.
They also accurately mapped the different cell types during the development of
the retina, as well as the genetic changes that occur during the early stages
of this developmental process.
"Beyond their 'age' - i.e., when they were generated during their
embryonic life - the diversity of neurons stems from their position in the
retina, which predestines them for a specific target in the brain,"
explains Fabre. "In addition, by predicting the sequential
activation of neural genes, we were able to reconstruct several differentiation
programs, similar to lineage trees, showing us how the progenitors progress to
one cell type or another after their last division."
Genetic Analysis of Stereoscopic Vision
It is established
that the stereoscopic vision of humans occurs due to a specific configuration
of the optic nerves with respect to their connections with the brain.
Essentially, the optic nerve originating from the right eye connects with the
left hemisphere of the brain and vice versa. However, a small fraction of the
neurons from the right eye, also make connections with the right hemisphere,
located on the same side of the brain. This results in overlapping of the
visual fields of both eyes, which allows 'depth-perception'
overlapping images are analyzed by the occipital lobe, which is the visual
processing center of the brain. This gives rise to stereoscopic or binocular
vision, which allows viewing of the surroundings in three-dimension (3D).
phenomenon, we have genetically and individually 'tagged' the cells in order to
follow each of them as they progress to their final place in the visual
says Quentin Lo Giudice.
The research team compared the genetic diversity of the two
neural populations, which led to the discovery of 24 new genes that could play
a crucial role in 3D vision in humans
. "The identification of these gene expression
patterns may represent a new molecular code orchestrating retinal wiring to the
Potential Applications of
Neuronal Migration in Regenerative Medicine
migration involves the passage of the neurons from the retina to the brain via
the optic nerve. The researchers carried out experiments to find the molecules
that guide this process of neuronal migration along the correct path. They
subsequently identified these molecules and found that these same molecules are
also responsible for the initial growth of axons. These axons are the long
thread like parts of nerve cells that conduct electrical impulses away from the
cell body to adjacent neurons through the synapse, which is the junction
between two nerve cells. The researchers also discovered 20 genes that are involved
in this process of nerve impulse transmission. This fundamental discovery is
likely to have important applications in the field of regenerative medicine.
Future Plans & Concluding Remarks
conclude that further in-depth knowledge about the molecules that guide axonal
growth will enable the development of therapies to treat nerve trauma
"If the optic nerve is cut or damaged, for example, by glaucoma, we
could imagine reactivating those genes that are usually only active during the
embryonic development phase. By stimulating axon growth, we could allow neurons
to stay connected and survive,"
explains Fabre, who is
planning a research project to explore these possibilities.
genetic stimulation of nerve regeneration could enable doctors to repair an
injured spinal cord
, which may have been damaged by
an accident. In fact, some initial clinical studies have already shown
promising results using this technique.
- Single-cell Transcriptional Logic of Cell-fate Specification and Axon Guidance in Early-born Retinal Neurons - (https://dev.biologists.org/content/146/17/dev178103)