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Published on: May 12, 2019
Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence
Ki-Jun Yoon1, Caroline Vissers2, Guo-Li Ming1,2,3,4
1Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA.
Neural progenitor cells (NPCs) precisely coordinate brain development through epigenetic and epitranscriptomic mechanisms. These regulatory systems predetermine cell fate early, ensuring the ordered generation of diverse neural cell types.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- Embryonic brain development involves sequential generation of diverse neural cell types from neural progenitor/stem cells (NPCs).
- NPCs transition through developmental stages, but the molecular control of this temporal coordination is not fully understood.
- Epigenetic mechanisms (chromatin, DNA methylation, histone modifications) and epitranscriptomics (RNA modifications) are implicated in neural development.
Purpose of the Study:
- To review advances in understanding the molecular regulation of sequential NPC lineage specification in the embryonic mammalian brain.
- To focus on the roles of epigenetic and epitranscriptomic mechanisms in coordinating NPC behavior.
- To discuss a model of epigenetic and transcriptional prepatterning in NPC developmental competence.
Main Methods:
- Review of recent studies on epigenetic and epitranscriptomic regulation in neural development.
- Analysis of findings related to lineage-specific gene transcript turnover in NPCs.
- Synthesis of information to propose a model for NPC developmental competence.
Main Results:
- Epigenetic and epitranscriptomic mechanisms play critical roles in coordinating NPC lineage specification.
- Rapid turnover of lineage-specific transcripts suggests early determination of NPC fate competence.
- Multiple regulatory systems cooperate to control NPC behavior.
Conclusions:
- Epigenetic and epitranscriptomic regulation are key to the precise temporal coordination of NPC differentiation.
- NPC developmental competence is established earlier than previously thought, controlled by prepatterning mechanisms.
- A coordinated interplay of regulatory systems ensures the ordered generation of neural cell types during embryonic brain development.
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