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Using color to track astrocytes in high resolution

Researchers from MIRCen partnered with École Polytechnique, the CNRS, Inserm and LOB to develop combinatorial labeling techniques wherein color and 3D and high-resolution imaging are used to demonstrate astrocyte plasticity during cerebral cortex development.

Published on 8 November 2019

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 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.

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