The Development of Astrocytes, in Color

Science

Astrocytes are neural cells whose role in brain function is increasingly studied. Karine Loulier, Jean Livet and their colleagues have, for the first time, elucidated the stages of their early development in the mouse cerebral cortex.

Sometimes bushy, sometimes slab-like, various forms of astrocytes can be found in the cerebral cortex. Astrocytes – nerve cells which belong to the glial cell group – have long been considered as mere support cells for neurons. The reality is that they play much more varied roles, namely in cerebral blood flow regulation and synaptic function.

Karine Loulier (Institute for Neurosciences of Montpellier*), Jean Livet (Institut de la vision**, Paris), and their colleagues*** are working to elucidate the early development stages of nerve cells, taking a particularly keen interest in astrocytes. Thanks to a technique in which their laboratories are specialized – the MAGIC Markers strategy – the researchers have, for the first time, succeeded in tracking the stages of astrocyte development, from the embryonic stage in which they are derived from progenitor cells, right up to three weeks after birth when they have matured. This technique involves marking several neural progenitor cells with distinct colors and then tracking what happens − in time and space − to the cells that they generate, especially the astrocytes.

© Clavreul et coll. Nat Comm 2019

Un arc en ciel mouvant

The MAGIC Markers transgenes are administered in utero to the brains of the embryos at Day 15 of their development – a point at which the cerebral cortex still contains a large number of progenitor cells. The application of an electrical current (electroporation) is used to introduce the transgenes into the progenitor cells. These transgenes code for several fluorescent proteins, and random rearrangements within each of the former create a combination of colors specific for each cell having "retrieved" several copies of these transgenes. These transgenes incorporate into the genome, which enables them to be preserved during the cell divisions and to obtain the identical color of all the daughter cells. The result therefore is several cell families (clones), which differ in color among themselves, but are each made up of sister cells of the same color. The next step then involved using ChroMS microscopy to obtain high-definition 3D images of astrocytes in development, images evocative of a rainbow in movement.

The team observed development in the form of three phases. First to take place is a colonization phase of the developing cerebral cortex in utero, following which – during the first week after birth – the astrocytes distribute themselves within the cortex at the same time as they proliferate. Their number doubles during this period and they already form a continuous network. The astrocytes then undergo a maturation period on the individual scale, up to Day 21 after birth (which is when the tracking stopped). "Combining the MAGIC Markers and ChroMS techniques has for the first time made it possible to simultaneously track the composition of several dozen astrocyte clones during brain development, explains Loulier. In addition to clarifying the various stages of colonization, expansion and maturation of cortical astrocyte development leading to the formation of a continuous network, our research offers an unprecedented view of the composition of these astrocyte families, thereby revealing their considerable diversity in terms of number, distinct subtypes and location in the cerebral cortex of developing mammals" she clarifies. The researcher now wishes to go further, verifying whether the development abnormalities of this glial network can be correlated with psychiatric disorders, such as autism and schizophrenia. A new chapter – which has already begun.

A revolution in brain imaging: ChroMS, a new microscopy technique bringing together color, 3D and high-resolution imaging (Only available in French) – report – 2 min 109 – © Ecole Polytechnique, 2019

Notes :

* unit 1051 Inserm/Université de Montpellier, ATIP-Avenir team Corticogenesis: diversity and plasticity of neural stem cells during brain development, in healthy and pathological settings, Institute for Neurosciences of Montpellier

** unit 968 Inserm/CNRS/Sorbonne Université, Neurogenesis and circuit development team, Institut de la vision, Paris

*** grouped within the Institut de la Vision, the Laboratory for Optics and Biosciences (unit 1182 Inserm/CNRS/Ecole Polytechnique, Palaiseau) and the Molecular Imaging Research Center, a preclinical research installation created by the CEA and Inserm, based at the CEA site in Fontenay-aux-Roses

Source : S Clavreul et coll. Cortical astrocytes develop in a plastic manner at both clonal and cellular levels. Nature communications, online edition of October 25, 2019. DOI: 10.1038/s41467-019-12791-5