Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Signaling and extrinsic forces leading to differentiation of neural crest cells to form ganglia of the peripheral nervous system

In plain English

AI plain-English summary

Nerve cells that will form the trigeminal ganglion—a key cluster of nerves in the head—rely on tiny cargo-carrying vesicles released by neighbouring embryonic cells to receive instructions on where to go and what to become. The project addresses a fundamental gap in developmental biology: how mechanical forces in the embryo’s local environment influence the production and contents of these small extracellular vesicles (sEVs), which shuttle microRNA signals between neural crest cells and placode cells. While scientists know that cell-to-cell signalling is essential for building cranial ganglia, the role of physical cues—such as tissue stiffness or compression—in controlling vesicle biogenesis and cargo selection is almost entirely unexplored. This is curiosity-driven fundamental science. If successful, it will reveal how mechanical and molecular signals cooperate to orchestrate cell migration and differentiation during embryonic development. In the longer term, understanding this mechano-molecular interplay could inform the design of sEV-based therapies—for example, engineering vesicles with precisely loaded microRNA cargoes to guide nerve repair or regeneration. Past fundamental work on embryonic cell communication has similarly laid the groundwork for regenerative medicine approaches now in clinical testing.

View original technical description
Interactions between cell from different tissues is essential for tissue morphogenesis. In vertebrates, the interaction between neural crest (NC) and placode cells (PC), is essential for cranial ganglia formation. However, the mechanism mediating their interplay remains largely unknown. Small extracellular vesicles (sEVs) have gained prominence for their role as miRNAs carriers during cell-cell communication. However, their biogenesis and selective miRNA cargo remains poorly understood, particularly regarding the influence of the ir microenvironment. Some evidence indicates that mechanical cues from the environment influence sEVs biogenesis and content. Given that mechanical cues are essential for NC development we propose to address whether and how local microenvironmental mechanics instruct sEVs production by NC to influence PC behavior during trigeminal ganglion morphogenesis and differentiation. To attain this, we will resort to our combined multidisciplinary experience in the study of these embryonic cell populations, tissue mechanics and sEVs; and the use of complementary in vivo and ex vivo approaches. This research has the potential to uncover fundamental insights into how mechano-molecular tissue interplay contributes to the spatiotemporal control of morphogenetic events such as cell migration and differentiation. In the long range, this information will contribute to refine and generate novel sEV-based therapeutics strategies.

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Researchers

Pablo Strobl-Mazzulla (EPMC Awardee)

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Original classification

Career Development Award

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