Asymmetric Cell Division Mechanisms in Epithelial Systems

Asymmetric cell division in epithelial tissues underpins the generation of cellular diversity and the maintenance of organised tissue architecture. In these systems, mitotic spindle orientation is coupled to cortical polarity cues to ensure that daughter cells inherit distinct fate determinants or occupy specific spatial positions. A conserved ternary complex comprising Gαi, LGN (Gpsm2) and NuMA directs the anchoring of astral microtubules to defined cortical domains, while transmembrane adhesion molecules such as E-cadherin and accessory factors like Annexin A1 provide positional information. The balance between planar and perpendicular division angles governs symmetric versus asymmetric outcomes, driving processes from epidermal stratification to organ morphogenesis. Disruption of these mechanisms can lead to loss of epithelial integrity, aberrant differentiation or tumour formation. Recent advances have illuminated upstream polarity cues, dynamic regulation of spindle-tethering complexes and links between cell-cycle progression and spindle alignment, offering novel therapeutic entry points for regenerative medicine and cancer biology.

Research from Nature Portfolio

Recent studies have identified Annexin A1 as an essential cortical polarity cue that interacts directly with LGN in mammary epithelial cells. Annexin A1 recruits LGN and NuMA to lateral cortex domains independently of Gαi, thereby stabilising Dynein–Dynactin attachment to astral microtubules and ensuring planar spindle alignment. Loss of Annexin A1 randomises division orientation and disrupts three-dimensional epithelial architecture. Earlier foundational work demonstrated that E-cadherin instructs spindle orientation by serving as a binding platform for LGN at cell–cell contacts. On mitotic entry NuMA competes LGN from E-cadherin, locally assembling the LGN–NuMA complex to align the mitotic spindle with intercellular adhesion sites. This mechanism couples adhesion dynamics to division orientation and is broadly conserved across mammalian epithelia.

Asymmetric Cell Division Mechanisms in Epithelial Systems publication trend

The graph below shows the total number of articles in asymmetric cell division mechanisms in epithelial systems across all publications each year (not limited to Nature Index journals).

Technical terms

Asymmetric cell division: A division yielding daughter cells with distinct sizes, contents or fates, critical for tissue patterning.

Mitotic spindle: The microtubule-based structure that segregates chromosomes during cell division and whose orientation determines cleavage plane.

Cell polarity: The spatial asymmetry of cellular components that provides directional cues for processes such as division and migration.

Astral microtubules: Microtubule arrays that radiate from spindle poles to the cell cortex, mediating spindle positioning.

LGN (Gpsm2): A cortical adaptor protein that binds Gαi and NuMA to anchor astral microtubules for spindle orientation.

Planar division: A mitotic division oriented parallel to the epithelial plane, generally producing two equivalent progeny and expanding the layer.

Perpendicular division: A mitotic division oriented orthogonally to the epithelial plane, often generating one basal progenitor and one differentiating cell.

Epithelial stratification: The multilayering of epithelial cells driven by regulated switches between planar and perpendicular divisions, enabling tissue thickening and maturation.

References

1. Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis. Nature Communications (2023).
2. Cell division orientation is coupled to cell–cell adhesion by the E-cadherin/LGN complex. Nature Communications (2017).
3. Meru co-ordinates spindle orientation with cell polarity and cell cycle progression. The EMBO Journal (2025).
4. AGS3 antagonizes LGN to balance oriented cell divisions and cell fate choices in mammalian epidermis. eLife (2023).