Brain development: Extracellular vesicles control cellular communication

Extracellular vesicles are tiny vesicles that are released by cells. They serve as small cargo ships with which the cells exchange messenger substances and thus communicate with each other. A recent publication in the journal Cell Reports has now shown that this form of cellular exchange also plays a central role in the development of the brain. "Our results underline the central role of vesicles in intercellular signaling during brain maturation and highlight their potential as mediators of complex cellular interactions and as targets for future therapeutic strategies," says Professor Silvia Cappello, head of the study, research group leader at LMU's Biomedical Center and member of the SyNergy Cluster of Excellence.

The team studied extracellular vesicles in various model systems, including neural progenitor cells, neurons, astrocytes, brain organoids and structured spheroids, each generated from pluripotent stem cells. This enabled the researchers to gain various new insights into how the small transport vesicles influence brain development.

Specific communication and dynamic protein composition

A key finding of the study is that extracellular vesicles enable specialized communication between different cell types. "We were able to show that the recipient cells are supplied with cargo from different donor cells and have specific uptake patterns," explains Cappello. This indicates that the vesicles specifically control the exchange of information between the cells.

The researchers also discovered that the composition of the proteins in the vesicles changes dynamically during brain development and depends on the cell population and the brain region. "This indicates that the biogenesis of the vesicles is strictly regulated and essential for their specific functions in the different cell types," says Cappello.

Transport to the cell nucleus

Using high-resolution live imaging techniques, the team was also able to show that vesicles even penetrate the nucleus of neural progenitor cells during cell division. "This discovery is particularly exciting as it suggests that extracellular vesicles control crucial processes not only in the cytoplasm but also at the nucleus level." As the study points out, the transported cargo consists not only of proteins, but also of transcription factors, such as YAP1, which are transferred directly into the recipient cells and trigger rapid transcriptional changes there. A particularly interesting example is the transcription factor YAP1, which is transported into the cell nucleus of recipient cells in this way and regulates gene expression there. "This ability of extracellular vesicles to transmit specific molecular signals to the cell nucleus opens up new perspectives for understanding complex cellular interactions in the brain," says Cappello.

According to the authors, these findings underline the central role of extracellular vesicles in brain development and could enable new therapeutic approaches for the treatment of neurological diseases in the long term.

Andrea Forero et al.: Extracellular vesicle-mediated trafficking of molecular cues during human brain development. Cell Reports 2024