Celf1 regulation of dmrt2a is required for somite symmetry and left-right patterning during zebrafish development.
RNA-binding proteins (RBPs) bind to numerous and diverse mRNAs to control gene expression post-transcriptionally, although the in vivo functions of specific RBP-mRNA interactions remain largely unknown. Here, we show that an RBP named Cugbp, Elav-like family member 1 (Celf1) controls expression of a gene named doublesex and mab-3 related transcription factor 2a (dmrt2a), which is essential for somite symmetry and left-right patterning during zebrafish development. Celf1 promotes dmrt2a mRNA decay by binding to UGU repeats in the 3'UTR of dmrt2a mRNA such that celf1 overexpression reduces the amount of dmrt2a mRNA, leading to asymmetric somitogenesis and laterality defects. Furthermore, blocking the Celf1-dmrt2a mRNA interaction by a target protector morpholino alleviates failures in somite symmetry and left-right patterning that are caused by celf1 overexpression. Our results therefore demonstrate that Celf1-dependent fine-tuning of dmrt2a expression is essential for generating bilateral symmetry of somites and left-right asymmetric patterning during zebrafish development.
Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Nara 630-0101, Japan. matsui@bs.naist.jp
Takaaki
T
Matsui
Akihiro
A
Sasaki
Naoko
N
Akazawa
Hifumi
H
Otani
Yasumasa
Y
Bessho
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D000067879:CELF1 Protein; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D055785:Gene Knockdown Techniques; D051379:Mice; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019170:Somites / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000067879:CELF1 Protein; C412365:CELF1 protein, zebrafish; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C486539:dmrt2a protein, zebrafish