Clavreul et al Nat Commun 2019 news image 1

Publicated in Nature Communications

Understanding how the brain develops requires tracing back the origin of its cellular constituents, the neurons and glial cells.  While the formation of neurons is quite well understood, that of glial cells, their main partners in many brain functions, still holds its share of mysteries. This is particularly the case for astrocytes, which constitute the largest population of glial cells in the brain. Initially considered to represent simple support cells, they actually have many other essential roles, including blood flow and synapse regulation. They are intriguing cells because of their organization as a continuous three-dimensional network and the variety of their morphological, molecular and functional properties.

To better understand how this network is set up during the development of the cerebral cortex, the site of the most elaborate nerve functions, researchers from Sorbonne University, Ecole Polytechnique, CNRS, INSERM and CEA grouped within the Institut de la Vision (IdV), the Laboratoire d'optique et biosciences (LOB) and the Laboratory of neurodegenerative diseases at the Molecular Imaging Research Center (MIRCen) have combined two approaches that they previously developed: the MAGIC Markers technique, which attributes colors to neural cells based on the expression of fluorescent proteins (Loulier et al, Neuron, 2014), and ChroMS microscopy, which associates color, 3D and high resolution (see CP of 10 April 2019, Abdeladim et al., Nat Commun 2019). The first approach creates a "color code" that identifies astrocytes resulting from the division of a same neural stem cell. The second one enables to visualize in 3D these groups (clones) of astrocytes in the mouse brain.

The combination of these two techniques has allowed the researchers to accurately characterize the composition of dozens of cortical astrocyte clones. Their work reveals the variable composition of these clones in terms of number and subtypes of astrocytes - a same neural stem cell being able to generate different subtypes of astrocytes - and their intricate organization reflecting rearrangements during development. Their study also clarifies the three phases of development of the cortical astrocyte network: colonization of neural tissue, proliferation and maturation. The results indicate that astrocytes show a plastic and dynamic behavior during these three stages. This developmental plasticity of astrocytes opens up new perspectives for our understanding of brain formation and of one of its essential cell type, astrocytes.