Balancing proliferation and differentiation in a developing organ is a complex act, especially when these two processes occur at the same time in the same space. The retina is an important interface between the body and the external world: it is located at the back of our eyes and receives and encodes all visual information, so that our brain can continuously process images of what the world has to offer. . “To achieve this function, the retina requires a precise balance of different types of neurons organized in several interconnected layers, each one receiving, grouping or filtering the visual input”, explains Elisa Nerli, first author of the study and researcher at the Gulbenkian Institute of Science. . . “The formation of the different neurons in the correct number and proportions is ultimately ensured by balancing cell proliferation and differentiation during development.”
By studying the development of the zebrafish retina, the team led by Caren Norden, principal investigator at the Gulbenkian Institute of Science, discovered that this balance depends on asymmetric divisions of progenitor cells on their way to the production of functional neurons. “We also found” – continues Nerli – “that the molecular regulation of this process is based on the Notch signaling pathway, since its inhibition interferes with the asymmetry of division. We were able to observe that Notch is distributed asymmetrically during cell division. Cell that inherits Notch signaling will continue to proliferate, while the other cell will enter a neurogenic lineage. ”
Overall, this study adds new insights to the fundamental understanding of how cell proliferation or differentiation decisions can regulate the development of the nervous system. Understanding how the balance between these processes is determined and maintained is important to better understand brain development, in health and in disease.
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This study was conducted primarily at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, and ended at the Gulbenkian Institute of Science. It was funded by the ERC Consolidator Grant (H2020 ERC-2018-CoG-81904) and Deutsche Forschungsgemeinschaft (NO 1068 / 5-1).
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