An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis

Area of Science:

• Cell Biology
• Developmental Neuroscience
• Pathology

Background:

• Entosis is a cellular process where live cells are engulfed by neighboring cells, observed in tumor contexts.
• The role of entosis in non-cancerous diseases, like microcephaly, remains largely unexplored.
• Microcephaly is a neurodevelopmental disorder characterized by a significantly smaller brain size.

Purpose of the Study:

• To investigate the potential role of entosis in the pathogenesis of microcephaly.
• To explore the cellular mechanisms underlying cell death in microcephaly models.

Main Methods:

• Utilized a mouse model with mutations in the microcephaly-associated gene Pals1.
• Observed cell-in-cell (CIC) structures during mitosis and cytokinesis.
• Applied ROCK inhibition and genetic elimination of Trp53.

Main Results:

• Pals1-mutant mice exhibited CIC structures and abnormal cell division in diminished cortical tissue.
• ROCK inhibition abolished CIC structures and normalized mitosis.
• Trp53 elimination rescued cortical size, reduced CIC structures, and decreased cell death.

Conclusions:

• Entosis represents a novel pathogenic mechanism contributing to microcephaly.
• Targeting entosis or related pathways may offer therapeutic strategies for microcephaly.