A mechanism for healthy brain development

( Image: Shutterstock)
( Image: Shutterstock)

Scientists at UCLouvain have discovered that the balance between two proteins plays a decisive role in brain development. The study is published in theAmerican Association for the Advancement of Science’s (AAAS) prestigious journal Science Advances.

During embryonic development, cells continuously receive numerous stimuli to which they react via intracellular signals.

Stem cells must both multiply and produce neurons. A good balance between proliferation and differentiation is necessary to avoid uncontrolled stem cell multiplication, but also to ensure sufficient neuron production.

A key question is to understand how these multiple, sometimes opposing, signals interact to guide the behavior of our cells in a coherent way to form healthy organs and individuals.

Alexia Cossard and two members of Prof. Yves Jossin’s laboratory at UCLouvain’s Institut des Neurosciences have demonstrated that, during brain development, a key interaction between MKL/SRF and Bcl6n proteins is decisive in ensuring the proper growth and positioning of brain cells.

In concrete terms, these two proteins induce opposite choices in the behavior of progenitor cells - which are not yet showing signs of differentiation - when they have to decide whether to multiply or produce neurons, but also whether to move within the tissue. What’s more, when these proteins meet, they cancel each other out. The result is an equilibrium resulting from a trial of strength between them.

Cells have several regulatory mechanisms to act in a controlled way. For example, stem cells receive numerous proliferation signals, and experimental models have shown that Bcl6 is a "global regulator", as it prevents the cell from responding to several of these signals. On the other hand, Bcl6 must be controlled. MKL/SRF then comes into play, inhibiting Bcl6 while Bcl6 also inhibits SRF. This mechanism, in which two signals inhibit each other, tilts the balance between choosing to multiply or differentiate into a neuron.

Yet we know that disturbances in these processes can contribute to health problems such as microcephaly, epilepsy, mental retardation and other brain disorders.

The researchers believe that this discovery could pave the way for new approaches to the diagnosis and treatment of brain diseases in children. Furthermore, the study of this mechanism in the adult brain, but also during the formation and function of other tissues, as well as in cancer cells, could lead to a better understanding of the general mechanisms of differentiation and proliferation control.

The study was published in the prestigious American scientific journal Science Advances, underlining its importance in the biomedical field.