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Key to Neurogenesis

Neural progenitor cells can differentiate into different cell types in the adult brain: into new neurons, but also into glial cells. In the study, it was shown that the transcription factor Pax6 causes a change in chromatin structure by interacting with the so-called BAF complex and thereby influences the fate of neural progenitor cells.

The formation of nerve cells is mainly restricted in mammals to the development phase and takes place in the adult stage only in a few regions of the forebrain. The usual case in the adult brain is the formation of supporting cells, also called glial cells. In fact, even stem cells that were transplanted as a therapy for neurodegenerative diseases usually develop into glial cells instead of the desired neurons.

The few regions of adult neurogenesis offer an opportunity to investigate just how neurons can be formed even in the adult brain. Both in the developing brain and in the adult brain numerous transcription factors are involved in neurogenesis. However, it is still unclear how the final differentiation of the progenitor cells is controlled at the molecular level.

One key mechanism in this process was elucidated by the team led by Jovica Ninkovic and Magdalena Götz of the Institute of Stem Cell Research. By searching for the interaction partners of the transcription factor Pax6, which plays a major role both in the development of the brain and in adult neurogenesis, the scientists showed that Pax6 interacts with the so-called BAF complex, which can alter the chromatin structure, and that this interaction determines the fate of the neural progenitor cells. Through the interaction, the chromatin is modified in such a way that certain genes that serve the regulation of neuronal differentiation become accessible.

As a result, the genes necessary for neuronal differentiation are more strongly expressed and the fates of neuronal cells – even in surroundings where otherwise only glial cells are formed – are stabilized. A loss of function of Pax6 or BAF – depending on the surroundings – leads to the formation of glial cells instead of neurons. Thus, the scientists describe for the first time certain molecular prerequisites of neurogenesis in the adult brain. This could be the basis for new therapies, e.g. to stimulate the formation of nerve cells in neurodegenerative diseases or after brain injuries and to replace damaged cells.

nerve cell or neuron is a cell that is specialized in signal transduction and synaptic transmission. Neurons are found in almost all multicellar animals. All of the nerve cells on an organism and the glial cells comprise the nervous system,



Diagram showing the interaction of transcription factors that decide the fate of neuronal progenitor cells. Source: HMGU