Scientists have discovered a novel way large embryonic cells divide without a complete contractile ring, challenging traditional models. Using zebrafish embryos, researchers identified a mechanical ratchet system involving microtubules and changing cytoplasmic stiffness. The findings, published in Nature, explain division in yolk-rich cells of various species.
Cell division, or cytokinesis, is a core process in biology, but its mechanics in early embryonic stages have puzzled researchers, particularly in animals with large, yolk-filled cells. A team led by Jan Brugués at the Cluster of Excellence Physics of Life at TUD Dresden University of Technology has uncovered a previously unknown mechanism that enables these oversized cells to split without relying on the standard actin-based purse-string ring.
Traditional models describe cells forming a contractile ring of actin protein at their midpoint, which tightens to separate into two daughter cells. However, in species such as sharks, platypuses, birds, and reptiles, the large yolk prevents the ring from fully closing. "With such a large yolk in the embryonic cell, there is a geometric constraint. How does a contractile band, with loose ends, remain stable and generate enough force to divide these huge cells?" questioned Alison Kickuth, lead author and recent PhD graduate from the group.
Focusing on zebrafish embryos, which feature sizable yolk-rich cells in early development, the researchers severed the actin band with a laser and observed it continuing to constrict. This indicated support along its length, provided by microtubules—another cytoskeletal component. Disrupting microtubules, either chemically or with an oil droplet obstacle, caused the band to collapse, confirming their role in stabilization and signaling.
Further experiments revealed that cytoplasmic stiffness varies with the cell cycle. During interphase, asters—expanding microtubule structures—stiffen the cytoplasm, anchoring the band. In the mitotic (M-phase), it fluidizes, permitting inward movement. Yet, this fluidity risks instability, which the band partially retracts but recovers through rapid embryonic cycles.
The process acts as a mechanical ratchet: instability during fluid phases is countered by restabilization in subsequent interphases, advancing division incrementally over multiple cycles until completion. "The temporal ratchet mechanism fundamentally alters our view of how cytokinesis works," Brugués stated. Kickuth added, "Zebrafish are a fascinating case, as cytoplasmic division in their embryonic cells is inherently unstable. To overcome this instability, their cells divide rapidly, allowing ingression of the band over several cell cycles by alternating between stability and fluidization until division is complete."
This discovery offers a new framework for cytokinesis in large, yolk-rich embryos across egg-laying species, highlighting the role of timed cytoplasmic properties in cellular processes. The study appears in Nature.
