Telophase correction refines division orientation in stratified epithelia

Area of Science:

• Developmental Biology
• Cell Biology
• Tissue Engineering

Background:

• Precise control of cell division orientation is crucial for balancing cell proliferation and differentiation during organogenesis.
• In the developing epidermis, planar divisions lead to symmetric outcomes, while perpendicular divisions result in asymmetric fate determination.

Purpose of the Study:

• To identify novel mechanisms regulating spindle orientation during mitosis.
• To investigate the role of specific proteins in correcting erroneous cell division orientations.
• To understand the impact of impaired division orientation on tissue architecture and cell differentiation.

Main Methods:

• Utilized live imaging microscopy in developing murine epidermis models.
• Investigated the function of the scaffolding protein LGN in telophase reorientation.
• Analyzed the contribution of adherens junction proteins (vinculin, α-E-catenin, afadin) to division fidelity.

Main Results:

• Identified a novel telophase reorientation mechanism that corrects oblique divisions towards a perpendicular axis.
• Demonstrated that LGN plays a role in this telophase correction, in addition to its known role in initial spindle positioning.
• Showed that tension-sensitive adherens junction proteins are essential for the fidelity of this corrective mechanism.
• Observed that failure of this correction leads to persistent oblique divisions, precocious differentiation, and disrupted tissue architecture.

Conclusions:

• Telophase correction provides plasticity in cell division orientation, allowing progenitors to adapt to local tissue needs.
• This mechanism is critical for maintaining epidermal tissue architecture and regulating differentiation.
• LGN and adherens junction proteins are key regulators of this late-stage division orientation control.