Cells in epithelial tissues, such as skin, are tightly packed together, forming cell-cell junctions that must be maintained for the tissue to function even as cells change shape when they divide. A cell undergoing the final stage of cell division—cytokinesis—pulls on its neighboring cells as it pinches into two cells. The neighboring cells must sense and respond to this physical stress to maintain contact and functional junctions with the new cells created by cytokinesis.
Understanding how neighboring cells affect the division of a particular cell within an epithelial tissue is the subject of research by the Miller Lab recently published in Developmental Cell.
“Our work demonstrates how manipulating the local tissue environment can impact the outcome of cytokinesis [cell division] even when the dividing cell itself is not directly perturbed. Understanding the relationship between cytokinetic and neighbor cell forces is essential to define the mechanisms underlying epithelial cytokinesis in development and disease.”
Proper cytokinesis is essential for development, tissue homeostasis, and tissue repair.
During cytokinesis, a ring of contractile protein filaments forms within the dividing cell that, as it contracts, pulls the cell membrane with it, forming a furrow that pinches inward until one cell becomes two.
In their research in frog embryos, the Miller lab showed that neighboring cells also assemble contractile protein filament arrays adjacent to the cytokinetic furrow, which restrain the rate of shape change in the dividing cell, and reinforce the cell junctions.
Using an optogenetic approach (i.e., light activates proteins when and where researchers want), the research team manipulated the levels of contractility that neighboring cells accumulated near the furrow of the dividing cell. Increasing contractility of neighboring cells slowed the rate at which the furrow ingresses or even led to cell division failures. Blocking the coupling between the dividing and neighboring cells sped up furrowing and disrupted the cell junctions.
They conclude that forces from the cytokinetic array in the dividing cell must be carefully balanced with restraining forces generated by neighbor cells to regulate the speed and success of cytokinesis and maintain the tissue’s integrity.
The research team was led by Jennifer Landino, a former postdoctoral scholar in the Miller group, who now leads her own group at Dartmouth’s Geisel School of Medicine. Other authors are Eileen Misterovich, former undergrad in the lab; Lotte van den Goor, former MCDB PhD student; Babli Adhikary, current MCDB graduate student; Shahana Chumki, former CMB PhD student, Lance A. Davidson, Professor at the University of Pittsburgh, who collaborated with the Miller Lab to generate a computational model of the process, and MCDB Professor Ann L. Miller.
The study:
Neighbor cells restrain furrowing during Xenopus epithelial cytokinesis,
Jennifer Landino, Eileen Misterovich, Lotte van den Goor, Babli Adhikary, Shahana Chumki, Lance A. Davidson, Ann L. Miller,
Developmental Cell, 2025, https://doi.org/10.1016/j.devcel.2025.03.010.
