Even our DNA can be recycled: the example of Cajal-Retzius cells

A recent publication in Developmental Cell, resulting from the work of the "Genetics and development of the cerebral cortex" team led by Alessandra Pierani, has shown that genes can be "hijacked" from their initial function in a given cell type, in order to fulfil a completely different function in another cell type. These results suggest a new approach to the diagnosis of rare diseases for which no mutation in the genes usually observed has been identified.

Published on 06.07.2023

Research Acceleration

At Institut Imagine (Inserm, AP-HP, Université Paris Cité), Alessandra Pierani's team is interested in the genetics and development of the cerebral cortex. As Frédéric Causeret, «  theme leader », explains, they are trying to establish how neurons acquire their identity, because there is a huge diversity of neuron types, functions and morphologies.

Frédéric Causeret's work focuses more specifically on Cajal-Retzius cells, a type of neuron that is crucial for the correct development of the cerebral cortex, and for which he has dissected the cellular content and, above all, identified the genes that are preferentially activated within this type of cell. Unexpectedly, these neurons express a whole set of genes normally linked to the development of a morphological characteristic observed in other cell types: multiciliation.

Multiciliation is a cellular process consisting of the growth of multiple motile cilia on the cell surface. Not all cells in the body are multiciliated, but they are found in the central nervous system of all vertebrates. It has been observed that the network of genes controlling multiciliation is highly conserved between organs and species.

Surprisingly, Cajal-Retzius cells, although expressing this gene network, are not multiciliated. Nevertheless, the team has confirmed that these genes play a crucial role in the maturation of these cells: the role of these genes has therefore been hijacked to give them a new function. How is this possible? Frédéric Causeret has established that this 'recycling' of the gene network depends on the stage of the cell's life during which these genes are expressed.

This new field of investigation, on the reorientation of highly conserved genes between species, allows us to think differently about the diagnosis of rare diseases. Indeed, this work illustrates how the same genes can be 'recycled' to fulfil very different functions in very different organs, and invites us to take a fresh look at the genetic variations identified in patients for whom it is still difficult to identify the gene responsible for the pathology.


doi: 10.1016/j.devcel.2023.05.011