Abstract
We recently reported that an RNA binding protein called Cugbp Elav-like family member 1 (Celf1) regulates somite symmetry and left-right patterning in zebrafish. In this report, we show additional roles of Celf1 in zebrafish organogenesis. When celf1 is knocked down by using an antisense morpholino oligonucleotides (MO), liver buds fail to form, and pancreas buds do not form a cluster, suggesting earlier defects in endoderm organogenesis. As expected, we found failures in endoderm cell growth and migration during gastrulation in embryos injected with celf1-MOs. RNA immunoprecipitation revealed that Celf1 binds to gata5 and cdc42 mRNAs which are known to be involved in cell growth and migration, respectively. Our results therefore suggest that Celf1 regulates proper organogenesis of endoderm-derived tissues by regulating the expression of such targets.
Highlights
Cugbp Elav-like family member 1 (Celf1), which is a member of the Celf family of RNA binding proteins, regulates gene expression at multiple post-transcriptional levels including alternative splicing and mRNA decay, and fine-tunes the amounts of proteins that are synthesized from its target mRNAs [1,2,3]
In the course of our investigation of other laterality organs such as liver and pancreas, we find an unexpected role for celf1 in zebrafish organogenesis; celf1 is essential for the formation of endoderm-derived organs
Since cardiac laterality was altered in celf1 knockdown (KD) embryos [13], we reasoned that the lateralities of endoderm-derived organs such as liver, pancreas and gut are altered in celf1 KD embryos
Summary
Cugbp Elav-like family member 1 (Celf1), which is a member of the Celf family of RNA binding proteins, regulates gene expression at multiple post-transcriptional levels including alternative splicing and mRNA decay, and fine-tunes the amounts of proteins that are synthesized from its target mRNAs [1,2,3]. Celf target mRNAs have been identified by several approaches such as the yeast three hybrid system [4], systematic evolution of ligands by exponential enrichment (SELEX) [5], RNA immunoprecipitation followed by microarray (RIP-Chip), and cross-linking immunoprecipitation. It has been reported that Celf is involved in the regulation of somite segmentation, muscle formation, and spermatogenesis in vertebrate development [6,11,12]. In the course of our investigation of other laterality organs such as liver and pancreas, we find an unexpected role for celf in zebrafish organogenesis; celf is essential for the formation of endoderm-derived organs
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