RGCC balances self-renewal and neuronal differentiation of neural stem cells in the developing mammalian neocortex

EMBO Reports, 2021 · DOI: 10.15252/embr.202051781 · Published: July 29, 2021

Regenerative Medicine Neurology Genetics

Simple Explanation

Neural stem cells (NSCs) initially divide to create more stem cells and later to produce neurons. The process that balances these two outcomes is not fully understood. This study shows that regulator of cell cycle (RGCC) is important for NSC self-renewal and neuronal differentiation by influencing cell cycle regulation and spindle orientation. RGCC defects could have etiological roles in human brain malformations.

Study Duration

Not specified

Participants

Mouse models, human embryonic stem cell (hESC)-derived cerebral organoid (hCO) models

Evidence Level

Not specified

Key Findings

1
RGCC is exclusively expressed in NSCs in the developing mammalian neocortex.
2
RGCC deficiency disrupts NSC cell cycle and spindle orientation, leading to pre-differentiation of NSCs and exhaustion of the NSC pool.
3
Knocking out RGCC causes reduction of size in human cerebral organoids.

Research Summary

This study investigates the role of Regulator of Cell Cycle (RGCC) in neural stem cell (NSC) self-renewal and differentiation during neocortical development. The researchers found that RGCC is exclusively expressed in NSCs and that its deficiency leads to impaired cell cycle progression, spindle misorientation, and premature differentiation of NSCs. The study concludes that RGCC is essential for maintaining the NSC pool and that RGCC defects could contribute to human brain malformations.

Practical Implications

Understanding Brain Development

The study provides insights into the molecular mechanisms regulating NSC fate during neocortical development.

Etiology of Brain Malformations

RGCC is identified as a potential etiological factor in human brain developmental malformations.

Potential Therapeutic Target

RGCC could be a potential therapeutic target for interventions aimed at correcting brain developmental disorders.

Study Limitations

1
The exact mechanisms by which RGCC regulates centrosome organization require further investigation.
2
Mutations in RGCC have not been identified in patients with brain malformations yet.
3
The study mainly focused on mouse models and human cerebral organoids, further in vivo human studies are needed.

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