Is Calcium Signaling the Bridge Between Unicellular and Multicellular Life?

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMJan 16 2025

The transition from single-celled organisms to multicellular life was a pivotal moment in evolutionary history, marking the emergence of complex communication systems that allow cells to coordinate behavior. In animals, sensory and motor functions rely on specialized cells like neurons and muscles, but the evolutionary origins of such systems remain poorly understood.

In a recent study published in Science Advances, researchers from the University of Bergen in Norway investigated electrical signaling and coordinated behavior in Salpingoeca rosetta, the closest unicellular relative of animals. Using a calcium indicator, the team uncovered novel cellular behaviors tied to electrical signaling, shedding light on how early multicellular organisms sensed and responded to environmental stimuli.

​​​​​​​Study: Electrical signaling and coordinated behavior in the closest relative of animals. Image Credit: Mopic/Shutterstock.com

Early Cellular Communication

Calcium signaling is a universal communication mechanism that facilitates interactions within and between cells across diverse life forms. In animals, it plays a central role in sensory-motor integration and drives critical processes such as signal transmission and movement.

Specialized excitable cells, such as neurons and muscles, depend on tightly regulated calcium dynamics—a feature thought to have emerged during early animal evolution.

Choanoflagellates, the unicellular relatives of animals, contain components of calcium signaling pathways. However, the functional role of these components in choanoflagellates remains unclear. These eukaryotes display complex behaviors like chemotaxis and feeding, hinting at the presence of primitive sensory systems.

While choanoflagellate colonies resemble early multicellular animals morphologically, their capacity for coordinated activity and cellular communication has remained largely unexplored.

The Study

This study focused on calcium-based signaling in S. rosetta, examining its role in cellular coordination. Researchers developed an S. rosetta line expressing the calcium-sensitive red fluorescent protein RGECO1, enabling them to visualize dynamic calcium changes during both unicellular and multicellular stages.

The experiments involved imaging spontaneous calcium transients—brief increases in free cytosolic calcium—and testing the effects of inhibitors such as gadolinium and verapamil.

They also involved growing cells in calcium-free media to assess the role of extracellular calcium and voltage-gated calcium channels. The team analyzed distinct patterns of calcium activity in solitary cells and multicellular colonies.

To explore environmental influences, the researchers manipulated bacterial abundance and measured calcium signaling. Depolarization triggered by potassium or adenosine triphosphate (ATP) application induced synchronized calcium responses, which were further confirmed using electric field stimulation.

High-speed imaging was used to link calcium transients to cellular shape changes, flagellar activity, and bacterial displacement, shedding light on the functional significance of calcium signaling. Genetic and pharmacological manipulations were also employed to confirm the role of voltage-gated calcium channels in regulating these signals.

Major Findings

The researchers discovered that S. rosetta exhibits calcium-dependent signaling tied to cellular coordination, offering insights into the evolution of multicellularity. Calcium transients were present in both unicellular and multicellular stages, with asynchronous activity dominating single cells and synchronized responses characterizing colonies.

In rosette-shaped colonies, synchronized calcium activity led to coordinated contractions and ciliary arrest, facilitated by intercellular communication through cytoplasmic bridges. The team also found that increased bacterial abundance heightened calcium signaling, suggesting a link between environmental stimuli and cellular responses.

High-speed imaging revealed a sequence of events following calcium surges: flagellar arrest, apical-basal cell contraction, and eventual resumption of activity. These behaviors occurred in both solitary cells and colonies but were more synchronized in the latter.

Pharmacological inhibition of voltage-gated calcium channels reduced calcium signaling, highlighting their central role in this process. Depolarizing agents, such as potassium and electric stimulation, further confirmed the capacity for external stimuli to drive coordinated cellular responses.

The spread of calcium signals in colonies suggested a regulated mechanism rather than passive diffusion, supporting the idea of early sensory-motor integration in primitive multicellular systems.

Broader Implications

These findings highlight evolutionary parallels between choanoflagellates and early multicellular animals, particularly in the use of calcium signaling to coordinate cellular activities. The ability to integrate and propagate environmental signals across cells may have been an early step toward the development of specialized tissues in animals.

Conclusion

Overall, this study demonstrated that calcium-based signaling was critical for coordinating cellular behavior in S. rosetta, enabling responses to environmental cues and synchronized actions within colonies.

By revealing parallels with early multicellular animals, the researchers shed light on possible evolutionary steps that led to complex sensory-motor systems.

These findings contribute to our understanding of how primitive signaling pathways influenced the transition to multicellular life, paving the way for future research in evolutionary biology.