The creation of astrocytes

Due to their fundamental function in the transmission of information, neurons are the great stars of the nervous system. However, more and more importance is given to the study of other cells that make it up and that with a lower profile play an essential role in brain organization: they are astrocytes, which historically were considered as mere components of structural support, and which are now known to play an important role in organizing the connections between neurons and the functioning of neural circuits.

To understand more about how astrocytes originate, why their functioning is sometimes altered and, finally, to be able to better address the development of treatments against certain neurological disorders, Micaela Sartoretti, Carla Campetella and Guillermo Lanuza, all three from the Fundación Instituto Leloir and the National Council for Scientific and Technical Research (CONICET), in Argentina, both institutions have carried out a study in which they have managed to determine the mechanism by which astrocytes are created and their diversity is regulated during embryonic development.

“Despite the fact that astrocytes are the most abundant cell type in the central nervous system, that they play fundamental roles for its functioning and that they are involved in various neurodegenerative pathologies, the mechanisms that guide their production are not known with certainty, nor what are the origins of its diversity”, Lanuza pointed out to the CyTA-Leloir Agency. And she added: “In this work we focus on the spinal cord, which houses the circuits responsible for body movement and the processing of sensory information.”

Neurons and glial cells such as astrocytes are produced from multipotent neural progenitor cells. To define whether the astrocytes that fulfill different roles and are located in different areas of the medulla have different embryonic origins, Lanuza and his team focused on a restricted group of progenitor cells in the neural tube (precursor of the central nervous system in the embryo). identified by the expression of the Dbx1 protein.

For this, through the use of molecular genetics in the mouse, they “tagged” all the cells produced by these Dbx1 progenitor cells and found that in addition to neurons, they generated astrocytes in more advanced stages of development. “We found that the population of astrocytes derived from Dbx1 progenitors is located with amazing precision in a defined place in the spinal cord, without intermingling with glial cells that are produced from other progenitors. In addition, these astrocytes express specific genes that differentiate them from those present in other regions of the bone marrow”, assured Lanuza, who is head of the Neural Development Genetics Laboratory of the Leloir Institute Foundation.

According to the scientist, the mapping of astrocytes found in the postnatal spinal cord indicates that different groups of embryonic cells are responsible for populating certain regions of the nervous system and not others. “We think that this mechanism is shaped to provide an optimal number of astrocyte subtypes to support the proper functioning of neurons in each spinal region and the assembly of synaptic connections between them,” he explained. And he went further: “This seems to be a general principle of astrogenesis throughout the nervous system.”

From left to right: Micaela Sartoretti, Carla Campetella and Guillermo Lanuza. (Image: FIL / CONICET)

But that is not all. The researchers also analyzed the role of the transcription factor Dbx1 (a protein that turns certain genes on or off) in the generation of astrocytes. For this, they obtained embryos from mice that had the Dbx1 gene deleted and found that their spinal cord contained a greater number of astrocytes, and that these were generated at the expense of neurons.

“These results indicate that Dbx1 is part of the genetic program that controls the ‘decision’ of neural progenitor cells to produce neurons or glial cells. We also found that the influence of Dbx1 on cell identities is due to changes in the intercellular communication pathway of Notch, usually involved in determining cell fates during development”, described Lanuza. And she concluded: “This study demonstrates that important aspects of astrocytic distribution and heterogeneity are determined in embryonic development. Understanding the basic principles of the origin of glial diversity will help to identify subclasses of astrocytes whose functioning is altered in various neurological disorders and in the face of damage to the nervous system”.

The study is titled “Dbx1 controls the development of astrocytes of the intermediate spinal cord by modulating Notch signaling”. It has been published in the academic journal Development, appearing on the cover of the magazine in its August issue, and has also been highlighted as outstanding research by the journal’s editors. (Source: CyTA-Leloir Agency)