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Distinct functions of alternatively spliced isoforms encoded by zebrafish mef2ca and mef2cb
M Ganassi1, S Badodi2, A Polacchini2
1University of Modena and Reggio Emilia, Department of Life Sciences, Italy; Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK.
Biochimica Et Biophysica Acta
|May 22, 2014
Summary
Alternative splicing (AS) fine-tunes the activity of zebrafish Mef2c proteins, mef2ca and mef2cb, crucial for muscle development and embryonic patterning. Different splice variants exhibit distinct biological functions and expression patterns during development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Alternative splicing (AS) generates diverse MEF2C protein isoforms in mammals, but their specific functions remain largely uncharacterized.
- Teleost fish have two MEF2C paralogues, mef2ca and mef2cb, which are essential for cardiomyogenic differentiation and myofibrillogenesis in zebrafish skeletal muscle.
Purpose of the Study:
- To investigate the functional significance of alternative splicing in zebrafish mef2ca and mef2cb paralogues.
- To determine how different splice variants of mef2ca and mef2cb impact muscle development and embryonic patterning.
Main Methods:
- Analysis of alternative splicing patterns in zebrafish mef2ca and mef2cb coding exons 4-6.
- Assessment of the biological activity of different splice variants through expression and over-expression studies.
- Gene expression analysis of early embryonic patterning genes.
Main Results:
- Zebrafish mef2ca and mef2cb undergo alternative splicing in exons 4-6, yielding variants with differential biological activity.
- The mef2ca isoform lacking exon 5 exhibits reduced transcriptional activity and is prevalent before muscle differentiation.
- Over-expression of mef2ca isoforms including exon 5 disrupts embryonic patterning, while mef2cbL isoform induces ectopic muscle formation.
Conclusions:
- Alternative splicing is a critical regulatory mechanism controlling Mef2c activity during zebrafish development.
- Differential expression and function of Mef2c splice variants play key roles in muscle development and embryonic patterning.