Extracellular vesicles (EVs) are small bubbles released by cells that function as vehicles for cellular communication and signal exchange. A recent study published in the journal Cell Reports has shown that this type of cellular interaction is also crucial for brain development. “Our discoveries emphasize the essential function of EVs in intercellular signaling throughout brain development, suggesting their potential as mediators of intricate cellular interactions and as targets for future therapeutic interventions,” states Dr. Silvia Cappello, the lead researcher and head of a research group at LMU’s Biomedical Center, as well as a member of the SyNergy Cluster of Excellence.
The research team examined extracellular vesicles using a variety of model systems, including neural progenitor cells, neurons, astrocytes, brain organoids, and patterned spheroids, all derived from pluripotent stem cells. This approach allowed the researchers to gain new insights into how these small transport bubbles play a role in brain development.
Specific communication and dynamic protein composition
A significant discovery from the study is that extracellular vesicles enhance targeted communication between various cell types. “We showed that receiving cells absorb cargo from different donor cells, each exhibiting distinct uptake patterns,” Cappello explains. This finding illustrates the specificity inherent in EV-mediated communication.
The researchers also found that the protein makeup of the vesicles changes throughout brain development and differs among various cell types and regions of the brain. “This variability indicates a carefully controlled process of EV formation that is essential for their specific functions within different cell types,” Cappello adds.
Transport to cell nucleus
Utilizing high-resolution live imaging methods, the team revealed that extracellular vesicles penetrate the nucleus of neural progenitor cells during cell division. “This discovery is particularly thrilling, as it suggests that EVs can affect vital cellular processes not just in the cytoplasm, but also within the nucleus.” The study showed that the cargo transported includes proteins and transcription factors, such as YAP1, which are directly delivered to recipient cells and prompt swift transcriptional adjustments. A key example is the transcription factor YAP1, which is moved into the nuclei of recipient cells and triggers transcriptional changes. “This capability of extracellular vesicles to convey specific molecular signals to the cell nucleus opens up exciting new avenues for understanding complex cellular interactions within the brain,” Cappello remarks.
The authors believe these findings highlight the crucial role of EVs in brain development and could lead to innovative treatment strategies for neurological disorders in the future.
