To
understand how the brain develops, one must first understand how its composing
cells come to be. Today, the development of neurons is largely elucidated
but that of glial cells, which assist nerve cells in many cerebral functions,
still holds secrets. This is particularly true for astrocytes, the most
populous of the brain's glial cells. Originally perceived as simple support
cells, astrocytes have since been shown to play numerous essential roles within
the brain, particularly in blood flow regulation and synaptic function. They
are intriguing cells, presenting a network-like three-dimensional structuration
and a variety of morphological, molecular and functional properties.
A team from MIRCen (IBFJ/CEA-DRF)
partnered with researchers from Sorbonne University, the École Polytechnique,
CNRS, INSERM, the Institut de la vision and the Laboratory of Optics and
Biosciences (LOB) to better understand how the astrocytic network develops in
the cerebral cortex, where the most elaborate brain functions take place.
Toward that goal, the multi-institutional team deployed two complementary
techniques: one called MAGIC Markers, which uses fluorescent proteins to
color label neuronal cells1;
and another called ChroMS microscopy, which crosses the use of colors
with 3D and high resolution imaging2.
The
first technique creates a "color code" that identifies astrocytes
differentiated from a same neural stem cell. The second enables the 3D
visualization of the clonally-related astrocytes in the mouse brain.
By
deploying them together, the researchers were able to precisely characterize
the composition of a number of clonally-related cortical astrocytes. They thus
revealed the variable composition of the clones, in terms of the number and the
sub-types of the astrocytes—with descendants of a same stem cell able to belong
to different sub-types—and their intricate organization, reflecting the ebb and
flow of changes during development. They also brought new light to the three
phases of the development of the astrocyte network in the cortex: nerve tissue
colonization, proliferation and maturation, showing that the astrocytes behave
in a plastic, dynamic manner during them.
This
developmental plasticity of astrocytes creates new opportunities to further our
knowledge on how the brain forms and how abnormalities in that process relate
to certain neurodegenerative or neurodevelopmental pathologies.
1 : Loulier K.et al. Multiplex lineage tracking with combinatorial labels. Neuron 2014, 81(3):505-20.
2 : Abdeladim L., et al. Multicolor multiscale brain imaging with chromatic multiphoton serial microscopy. Nature Communications 2019, 10(1):1662.