Early genetic development of the brain mapped

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Sten Linnarsson. Photo: N/A

– It is the first comprehensive study of brain development with a focus on gene regulation. In the past, there have been studies that have largely always focused on the cortex, i.e. the cerebral cortex. Our study is a systematic mapping of the entire brain so that you can compare all regions with each other, says Sten Linnarssonprofessor of molecular systems biology at Department of Medical Biochemistry and Biophysics at Karolinska Institutet and research leader for the study.

When the brain begins to develop in the early embryo, it begins with something that can be likened to a tube, where the walls of the tube will develop into the brain and the fluid-filled center of the tube will become the ventricles, the cavities of the brain.

Rapid development in the brain early in the fetus

Between weeks 6 and 13 of pregnancy, a rapid specialization of the cells in the walls of the tube takes place. It happens through a very advanced cascade reaction where substances are secreted that signal the first cells to develop in a certain way. These cells then secrete new signals that direct the next step in cell development and so on.

The signals activate genes that produce protein which is what specializes the different cell types and which also act as new signals.

– It is this process, how, in what order and in which cell types genes are activated during this process where the brain is formed that we have studied. We wanted to follow the process from DNA to RNA, to the protein in each step, says Sten Linnarsson.

The research has been carried out with a method that can measure both active regions on DNA and formed RNA strands in individual cells. The researchers have then put the puzzle together and can now present a map of how it is done.

Part of larger Swedish project

The research is part of the larger Swedish project “Human Developmental Cell Atlas” where various research groups have studied the genetic development of the brain, heart, lungs and so on. The research in the project is now moving forward and the researchers are using the maps to find answers to what went wrong with illness and, by extension, how it can be treated.

– We are now studying the occurrence of brain cancer in children. It is fortunately an uncommon disease, but of the various diseases that lead to death in children, it is one of the more common. We study the tumors that arise during the brain’s embryonic development and use the atlas to try to understand which mechanisms of normal development have gone awry and how this drives tumor formation and tumor growth, says Sten Linnarsson.

The research was funded by the Erling-Persson Family Foundation, the Knut and Alice Wallenberg Foundation, the Foundation for Strategic Research and EC Horizon 2020. Sten Linnarsson is a scientific advisor to Moleculent, Combigene and the Oslo University Center of Excellence in Immunotherapy. He and first author Camiel Mannens are also shareholders in EEL Transcriptomics AB, which owns intellectual property rights to EEL-FISH.

publication

“Chromatin accessibility during human first-trimester neurodevelopment” Camiel CA Mannens, Lijuan Hu, Peter Lönnerberg, Marijn Schipper, Caleb C. Reagor, Xiaofei Li, Xiaoling He, Roger A. Barker, Erik Sundström, Danielle Posthuma, Sten Linnarsson. Nature, online May 1, 2024, doi:10.1038/s41586-024-07234-1