How cells utilize electric fields to guide their migration during embryonic development.
As an embryo develops, cells constantly communicate to organize into tissues and organs. This process requires cells to interpret various environmental signals, which can be chemical or mechanical. However, these signals alone do not fully explain how cells migrate collectively. A growing body of evidence suggests that embryonic electric fields also play a role in guiding cell movement. Until now, the origins and mechanisms behind these electric fields within embryos remained unclear.
“We have characterized an endogenous bioelectric current pattern, which resembles an electric field during development, and demonstrated that this current can guide migration of a cell population known as the neural crest,” highlights Dr. Elias H. Barriga, the corresponding author who led the study.
Dr. Barriga and his team began their research on the neural crest at the Gulbenkian Institute of Science (IGC) in Oeiras, Portugal, before continuing their work in Dresden, where they established a research group within the Cluster of Excellence Physics of Life.
The neural crest is a crucial component of embryonic development. This group of cells gives rise to the bones of the face and neck, as well as parts of the nervous system. Dr. Barriga and his team discovered that during development, neural crest cells are guided by internal electric fields, functioning much like drivers responding to the signals of a traffic warden.
The group discovered that through this process, known as electrotaxis, cells can sense direction from electric fields generated inside the embryo and move accordingly. This observation had been previously limited mostly to the study of cultured cells, but now was demonstrated within a developing embryo. But an important question remained unanswered: How are the cells interpreting these currents and translating them into directional movement?
Decoding Cellular Responses to Electric Fields
To answer this question, Dr. Barriga and his team identified an enzyme known as voltage-sensitive phosphatase 1 (Vsp1) found in neural crest cells. Due to the versatile structure of Vsp1, it seemed capable of both sensing and transducing electrical signals. To confirm that Vsp1 is required for electrotaxis, the researchers created a defective version of the enzyme and showed that collective electrotaxis was impaired in cells injected with this copy.
“For me, applying tools I developed to target gene expression in the context of bioelectricity was highly rewarding, and I look forward to its potential being fully exploited,” highlighted Dr. Sofia Moreira, a postdoctoral scientist who worked on the study. Contrary to expectations, Vsp1 did not appear to be relevant for movement itself, but instead could specifically convert electric current gradients into directional and collective migration.
This is a unique observation, as most enzyme sensors are required for movement itself, making it difficult to study their role in guiding direction. Going one step further, the authors also proposed how the electric fields may form; through the mechanical stretching of a region known as the neural fold. As the cells in this region stretch, this causes activation of specific ion channels, resulting in a voltage gradient. Then, when cells encounter this gradient, Vsp1 transforms the electrical signals into a directional cue, telling the cells which way to go, and collective cell migration results.
This is the first experimental evidence to suggest that electric fields emerge along the path where neural crest cells migrate, and to explain their mechanism of origin. These discoveries highlight the valuable contribution that bioelectricity provides during embryonic development.
Implications for Developmental Biology and Beyond
By advancing our knowledge of electrotaxis within a living animal, this research opens new possibilities for mimicking developmental processes in the lab, with accuracy greater than ever before.
The first author of the study, postdoctoral scientist Dr. Fernando Ferreira notes “This paper bridges an important, decades-old gap in bioelectricity research, and it is deeply rewarding to be part of the ongoing renaissance in developmental bioelectricity”. However, research into the mechanisms of electrotaxis is still ongoing.
“In a broader perspective, we have now introduced another player into the intricate process of tissue morphogenesis,” notes Dr. Barriga. “The question is now, how does this fit into already established frameworks of mechanical and chemical cues during embryogenesis?”
Beyond development, similar mechanisms might also exist during wound healing and cancer progression. Understanding how electric fields guide cell migration could even inspire potential novel strategies in tissue engineering and regenerative medicine. However, further research is required to expand on the role of electric fields in cellular behavior, and increase our understanding of the physics behind living systems.
Reference: “Stretch-induced endogenous electric fields drive directed collective cell migration in vivo” by Fernando Ferreira, Sofia Moreira, Min Zhao and Elias H. Barriga, 17 January 2025, Nature Materials.
DOI: 10.1038/s41563-024-02060-2
This work was supported by grants from the European Research Council Starting Grant (ERC-StG) under the European Union’s Horizon 2020 research and innovation programme, grant agreement no. 950254 (to E.H.B.); The European Molecular Biology Organization (EMBO) Installation Grant, project no. 4765 (to E.H.B.); EMBO Young Investigator program, project no. 5248 (to E.H.B.); EMBO postdoctoral fellowship, ALTF 27-2020 (to F.F.); La Caixa Junior Leader Incoming, no. 94978 (to E.H.B.); and Fundação para a Ciência e a Tecnologia (FCT) postdoctoral fellowship, 2020.00759.CEECIND (to S.M.). Research by E.H.B. was also supported by the IGC, Fundação Calouste Gulbenkian (FCG), start-up grant I-411133.01, and from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2068, 390729961), Cluster of Excellence Physics of Life of TU Dresden.
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