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Published on: January 26, 2018
CELF2-dependent RNA Regulation Supports Cortical Architecture and Synaptic Stability During Early Brain Development
Ishana Syed1,2, Jing Jiang3, Su-Hyuk Ko1,2
1Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.
The RNA-binding protein CELF2 (CUGBP Elav-like family member 2) is essential for brain development. Loss of CELF2 impairs neuronal maturation and cortical organization, highlighting its role in neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- RNA regulation is crucial for neurodevelopment.
- The role of CELF2 (CUGBP Elav-like family member 2) in the developing brain is unclear.
- CELF2 is an RNA-binding protein involved in splicing and mRNA regulation.
Purpose of the Study:
- Investigate the function of CELF2 in neurodevelopment.
- Determine the impact of CELF2 loss on brain structure and function.
- Elucidate the molecular mechanisms underlying CELF2's role.
Main Methods:
- Constitutive Celf2 knockout mouse model.
- Bulk and single-nucleus RNA sequencing.
- Histological analysis and functional studies in C. elegans.
Main Results:
- Celf2 knockout mice exhibit neonatal lethality, impaired neuronal maturation, and disrupted cortical organization.
- CELF2 loss leads to widespread transcriptional dysregulation and reduced exon inclusion in neurodevelopmental transcripts.
- Reduced Camk2a transcript and protein levels were observed, with CELF2 binding to Camk2a 3'UTR.
Conclusions:
- CELF2 is a critical post-transcriptional regulator for neuronal maturation and brain architecture.
- Disruption of CELF2 function contributes to neurodevelopmental disorders.
- CELF2 plays a conserved role in synaptic maturation.
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