Published: 2021-07-28 17:22 | Updated: 2021-07-28 17:23

Fetal development of the brain identified down to the smallest detail

Illustration of brain.
Illustration: Getty Images.

Researchers at Karolinska Institutet have developed a detailed molecular atlas of the fetal development of the brain. The study published in the top journal Nature is based on so-called single-cell technology and has been done on mice. In this way, researchers have identified almost 800 different cells that are active during fetal development – many times more than previously known.

Sten Linnarsson in his lab at MBB.
Sten Linnarsson. Photo: Ulf Sirborn

"Brain development is well described and the main cell types are known. What is new about our atlas is the high resolution and detail," says Sten Linnarsson, head of research and professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.

In their work, the researchers followed the brain development of the mice from day seven, when the brain is just forming, to the end of pregnancy on day 18.

Using single-cell technology, they were able to identify the detailed composition of the brain during fetal development: what cell types exist, how many cells of each type, and how this changes at the various stages of development.

The researchers also studied the activity of genes in each individual cell and classified cells based on these activity patterns.

Molecular atlas

The result is a molecular atlas that accurately shows how all cells in the brain develop from the early embryo. For example, it can be seen how early neural stem cells first increase and then decrease in number, to be replaced by transitional forms in several waves that eventually mature into ready-made neurons. 

The researchers also show how early stem cell lines branch and give rise to several different types of mature cells, much like a family tree.

The current study was led by doctoral student Gioele La Manno – now a researcher in Lausanne, Switzerland – and Kimberly Siletti, a postdoctoral researcher in Linnarsson's group. The study includes the international Human Cell Atlas (humancellatlas.org) initiative, which aims to identify all cells in the human body.

Specific cells in the brain

The next step in the researchers' work is therefore to create atlases of the human brain, both in adults and during fetal development.

"Atlases like this are of great importance for research into the brain, both to understand brain function and its diseases. Cells are the body's basic building blocks and the body's diseases are always expressed in specific cells. Genes that cause serious diseases are found in all of the body's cells, but they cause disease only in specific cells in the brain," says Sten Linnarsson.

The study has been funded with grants from, among others, the Knut and Alice Wallenberg Foundation, the Erling-Persson Family Foundation, the Torsten Söderberg Foundation, the Brain Foundation, and the Foundation for Strategic Research. Researchers at SciLifeLab, Stockholm University, and research institutes in Switzerland and the US have also formed part of the study team.

Publication

"Molecular Architecture of the Developing Mouse Brain", Gioele La Manno, Kimberly Siletti, Alessandro Furlan, Daniel Gyllborg, Elin Vinsland, Alejandro Mossi Albiach, Christoffer Mattsson Langseth, Irina Khven, Alex R. Lederer, Lisa M. Dratva, Anna Johnsson, Mats Nilsson, Peter Lönnerberg, Sten Linnarsson. Nature, online 28 July 2021, doi:10.1038/s41586-021-03775-x.