Long-term live imaging sheds light on human brain development

Source: https://bsse.ethz.ch/news-and-events/d-bsse-news/2025/06/long-term-live-imaging-sheds-light-on-human-brain-development.html Parent: https://bsse.ethz.ch/news-and-events/d-bsse-news.html?AUTHOR=Q2Fyb2xpbiBBcm5kdCBGb3BwYQ&path=L2NvbnRlbnQvc3BlY2lhbGludGVyZXN0L2Jzc2UvZGVwYXJ0bWVudC9lbi9uZXdzLWFuZC1ldmVudHMvamNyOmNvbnRlbnQvcGFyL25ld3NmZWVkXzQzMTg

Scientists led by Barbara Treutlein have developed a powerful new way to watch how tiny lab-grown human brain models - called brain organoids - form and grow over time. Using advanced light sheet microscopy and fluorescent markers, researchers tracked individual cells and their structures over several weeks, revealing in unprecedented detail how the early brain shapes itself. A key finding is the importance of the extracellular matrix, helping the organoids grow more organised brain regions.

In combination with single-cell RNA sequencing and spatial proteomics along with  lightsheet imaging, the team quantified multiscale changes as the tissue developed key brain regions by labelling and imaging different proteins inside the cells. They discovered that a supportive gel-like substance called extracellular matrix (ECM), often used to help grow organoids to mimic the natural support structure in human brains, plays a critical role in shaping brain structure and its regional identity. Organoids grown without this matrix developed differently, showing rather the traits of different brain regions and altered cell types. The scientists conclude that mechanosensitivity plays a central role during brain development: the cells are guided by the matrix and its mechanical forces, determining their form and function in specific brain regions.

“Our work will pave the way for understanding how molecular and mechanical information is integrated to specify different brain regions with their characteristic morphologies and unique functional identities.”

Akanksha Jain, postdoctoral researcher in the Quantitative Developmental Biology group of Barbara Treutlein.

\ \ \ The study which was published by Nature, also highlights the importance of specific genes and signalling pathways - like WNT and Hippo (YAP1). These signals influence how the brain tissue and cells organise into specific brain regions, offering insight into both normal development and potential developmental disorders.\ This work opens a new window into understanding how the human brain forms and may help scientists study brain diseases and test treatments in more realistic models.

Find original article in Nature:

Jain, A, Gut, G, Sanchis-Calleja, F et al. (2025) external page Morphodynamics of human early brain organoid development. Nature, DOI 10.1038/s41586-025-09151-3

Learn about research in the Quantitative Developmental Biology lab led by Barbara Treutlein.