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Alternative splicing controls pan-neuronal homeobox gene expression
Eduardo Leyva-Díaz1,2, Michael Cesar3, Karinna Pe3
1Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA; eleyva@umh.es.
Genes & Development
|December 27, 2024
Summary
The study reveals how the UNC-75/CELF splicing factor directs pan-neuronal expression of the CEH-44/CUX gene in C. elegans neurons. This process ensures neuronal identity and excludes a Golgi protein from the nervous system.
Area of Science:
- Developmental Biology
- Neuroscience
- Molecular Biology
Background:
- The CUT homeobox gene CEH-44/CUX is crucial for pan-neuronal gene expression in C. elegans.
- CEH-44/CUX and the Golgi-localized protein CONE-1/CASP are encoded by a complex locus.
- Regulation of this complex locus for pan-neuronal expression is not well understood.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling pan-neuronal expression of CEH-44/CUX in C. elegans.
- To elucidate how alternative splicing directs gene expression within the nervous system.
- To understand the cellular specificity of Golgi apparatus composition.
Main Methods:
- Utilized RNA splicing factor UNC-75, the C. elegans homolog of vertebrate CELF proteins.
- Analyzed the cone-1&ceh-44 locus during embryogenesis and neuronal differentiation.
- Investigated the spatial specificities of golgin proteins.
Main Results:
- Pan-neuronal expression of CEH-44/CUX is controlled by the RNA splicing factor UNC-75/CELF.
- During embryogenesis, only CONE-1/CASP is produced in all tissues.
- Postmitotic neurons specifically produce CEH-44/CUX via UNC-75/CELF-mediated alternative splicing, excluding CONE-1/CASP.
Conclusions:
- UNC-75/CELF-mediated alternative splicing directs pan-neuronal gene expression and establishes neuronal identity.
- This splicing mechanism excludes a conserved golgin from the nervous system.
- Findings reveal novel insights into neuronal development and Golgi apparatus specificity.
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