Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis

Area of Science:

• Cell biology
• Developmental biology
• Biophysics

Background:

• Hertwig's rule describes cell division orientation along the interphase cell's long axis, crucial for tissue development.
• Epithelial cell shape is influenced by adhesion, stress, and polarity pathways, but mechanisms for sensing this shape during division are unclear.
• During mitosis, epithelial cells round, complicating the inheritance of interphase shape information for division orientation.

Purpose of the Study:

• To investigate the mechanisms by which epithelial cells sense their interphase shape to orient cell division.
• To identify the molecular players and structures involved in this shape-sensing process.
• To understand how division orientation is maintained as cells transition to mitosis.

Main Methods:

• Utilized Drosophila epithelia as a model system.
• Investigated the role of tricellular junctions (TCJs) in orienting cell division.
• Employed genetic manipulation, live imaging, and computational simulations.
• Focused on the Dynein-associated protein Mud and the Pins/Gαi pathway.

Main Results:

• Tricellular junctions (TCJs) localize force generators that pull on astral microtubules, orienting cell division via the Mud protein.
• This orientation mechanism operates independently of the classical Pins/Gαi pathway.
• TCJs act as spatial landmarks during mitotic rounding, encoding interphase cell shape anisotropy to guide division.
• Shape and mechanical strain sensing by TCJs arise from their distribution geometry within epithelial tissues.

Conclusions:

• TCJs are key regulators of cell division orientation in Drosophila epithelia.
• TCJs integrate geometric and mechanical cues from the tissue environment to orient division.
• Beyond barrier functions, TCJs act as critical polarity cues for epithelial morphogenesis and tissue mechanics.