by Researchers from the University of Exeter in the United Kingdom have made a remarkable discovery, uncovering a new pathway of intercellular signal sharing in zebrafish. The team’s findings challenge the conventional understanding of cellular responsiveness solely based on receptor expression. Published in the journal Nature, their study titled “Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish” sheds light on the complex mechanisms of ligand-receptor complex transport via specialized protrusions.
Cellular communication plays a crucial role in embryonic development, primarily occurring through chemical signaling. In the zebrafish embryo, the Wnt–planar cell polarity (PCP) pathway is responsible for regulating tissue polarity and cell migration. The researchers focused on understanding the role of chemical signaling in this process.
By using fluorescent tagging, the scientists were able to track the movement of Wnt5b and Ror2, which are key components of the Wnt-PCP signaling pathway. Remarkably, they found that these active complexes were transported between cells via specialized protrusions called cytonemes. Cytonemes are tubular or tubulovesicular structures that extend beyond the cell edge, allowing them to interact with neighboring cells.
What was particularly intriguing is that the transferred complexes maintained their functionality, even when the receiving cells lacked functional Ror2 receptors. This challenges the conventional view of tissue responsiveness, which has primarily been focused on receptor expression. The discovery of cytoneme-mediated transfer of signaling complexes between cells introduces a previously unknown method of intercellular communication.
In order to understand the roles of the receptors Ror1 and Ror2, the researchers used zebrafish lacking these receptors, as well as double mutants. They discovered that Wnt5b-Ror2 protein signaling in the sender cells influenced the formation of cytonemes, resulting in fewer but longer tubulovesicular structures.
The study demonstrated that Wnt5b-Ror2 complexes transferred via cytonemes maintained their activity in target cells, activating intercellular signaling. This had significant effects on the zebrafish’s early developmental stages, influencing convergence, extension, and gene expression.
The implications of this groundbreaking discovery are vast. Uncovering a novel cell-to-cell communication mechanism in embryogenesis could have important clinical relevance in understanding human embryogenesis, prenatal development, disease states, congenital disabilities, and intercellular communication in cancer cells.
While the study presents an extraordinary breakthrough, further research is necessary to validate and replicate these findings. Replication of the results will be of utmost importance, as well as exploring other mechanisms related to cytoneme-mediated transfer, such as the method for receiving cells to intake cytoneme-delivered proteins or the factors that contribute to the generation of longer cytonemes.
If confirmed, this previously unknown cellular signal-sharing capability would require extensive research to comprehend its implications on previous studies and its potential applications in various fields of science and medicine. The discovery has opened up new avenues for understanding intercellular communication, signaling pathways, and the complex mechanisms that govern embryonic development.
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1. Source: Coherent Market Insights, Public sources, Desk research
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