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Published on: May 8, 2020
Neural peer pressure: intercellular dynamics and emergent phenotypes in the mosaic Rett syndrome brain
Jarno Koetsier1,2, Chris P Reutelingsperger3,4, Leopold M G Curfs4
1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. jarno.koetsier@maastrichtuniversity.nl.
Cell Communication and Signaling : CCS
|June 17, 2026
Summary
Female brain development creates a mosaic of cells with different active X chromosomes. In Rett syndrome, cell interactions, not just individual cell defects, drive complex brain phenotypes and intermediate cell states.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Female embryogenesis involves random X chromosome inactivation, creating cellular mosaics.
- X-linked disorders like Rett syndrome result in brains with both mutant and wildtype cells.
- These cell populations interact via extracellular vesicles, biomolecules, and direct contact.
Purpose of the Study:
- To investigate the influence of cell-cell communication on brain development in mosaic X-linked disorders.
- To explore emergent behaviors arising from interactions between mutant and wildtype cells.
- To understand the spectrum of cellular phenotypes in mosaic Rett syndrome brains.
Main Methods:
- Analysis of cellular interactions in mosaic X-linked neurological disorder models.
- Investigating intercellular communication mechanisms (extracellular vesicles, biomolecules, cell contact).
- Characterizing the range of cell states beyond a simple dichotomy.
Main Results:
- Mutant and wildtype cell populations in mosaic brains influence each other bidirectionally.
- Interactions lead to emergent behaviors not explained by cell-autonomous effects alone.
- Evidence suggests a spectrum of intermediate cell phenotypes, not just two discrete states.
Conclusions:
- Cell population-level dynamics are crucial for understanding mosaic conditions.
- Focusing on intercellular communication is key to advancing Rett syndrome research.
- Therapeutic strategies may need to target cell interactions for effective treatment.
