Mechanism Behind Tissue Coordination in Embryonic Growth Identified

The development of an animal from a single cell is a process that requires incredible precision. As an embryo grows, different tissues, such as those comprising muscles, nerves, and various organs, must all form and expand at a synchronized pace while maintaining their correct positions relative to one another. While this harmonious growth is essential for shaping a functional body, the underlying mechanisms that orchestrate it, remain largely unknown.

To address this challenge, scientists have often looked to other fields for inspiration and useful techniques. For example, a concept from engineering known as ‘formation control’ provides a framework for analyzing how groups of agents, such as drone swarms or flocks of animals, can maintain their collective spatial arrangement as they move. Though powerful, this idea had never been applied to the growth of multicellular organisms—until now.

In a recent study, a research team led by Assistant Professor Toru Kawanishi of the School of Life Science and Technology, Institute of Science Tokyo (Science Tokyo), Japan, in collaboration with Professor Sean Megason at Harvard Medical School, USA, has unveiled a remarkable mechanism by which tissues in zebrafish coordinate their growth during embryonic development. Their work, published in Volume 11, Issue 31 of the journal Science Advances on July 30, 2025, focused on three midline tissues in zebrafish embryos—the notochord, floorplate, and hypochord—that must grow and elongate together while maintaining precise alignment during the formation of the animal’s body axis.

Using high-resolution live imaging and mathematical modeling, the researchers discovered that the floorplate and hypochord tissues follow the notochord, which serves as the leader. However, rather than growing through the simple addition of new cells at one end, these follower tissues employ a sophisticated migration strategy. Specifically, follower cells collectively crawl along the extending notochord’s surface in response to a gradient of fibroblast growth factor signaling molecules. This process causes slight mechanical stretching, which stimulates cell division through a mechanosensory protein called Yap.

Through careful experiments, the researchers found that cells in the tail migrate more actively than those closer to the head, ensuring that mechanical forces are distributed evenly throughout the tissue. This prevents gaps from forming while allowing fast and synchronized growth. Computer simulations confirmed that this ‘graded migration’ pattern was essential for maintaining tissue integrity during the elongation of the midline tissues.

Moreover, at the posterior end where new growth occurs, the researchers discovered that strong adhesive connections exist between tissues, mediated by the cadherin 2 protein. This adhesion acts as a fine-tuning mechanism, allowing the follower tissues to adjust their elongation speeds in real time to match the leader tissue, even when their intrinsic growth rates differ.

Notably, these leader-follower mechanisms were all successfully replicated using a mathematical model based on formation control. “Our study introduces a new design principle for coordinated tissue growth in embryonic development, showing that concepts from control theory, including formation control, can be applied to biological systems,” highlights Kawanishi.

Overall, this research provides insights that could eventually inform tissue engineering approaches and help scientists understand developmental disorders involving problems in tissue coordination. “Our findings open new avenues for understanding how complex tissue architectures are built and maintained, with potential relevance to other organs and species,” concludes Kawanishi.

Reference: Kawanishi T, Sushida T, Tsai TYC, Takeda H, Megason SG. Formation control between leader and migratory follower tissues allows coordinated growth. Science Advances. 2025;11(31):eads2310. doi: 10.1126/sciadv.ads2310

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