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Zebrafish cypher is important for somite formation and heart development
- Source :
- Developmental Biology, 299(2), 356-372. Academic Press
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- Mammalian CYPHER (Oracle, KIA0613), a member of the PDZ-LIM family of proteins (Enigma/LMP-1, ENH, ZASP/Cypher, RIL, ALP, and CLP-36), has been associated with cardiac and muscular myopathies. Targeted deletion of Cypher in mice is neonatal lethal possibly caused by myopathies. To further investigate the role of cypher in development, we have cloned the zebrafish orthologue. We present here the gene, domain structure, and expression pattern of zebrafish cypher during development. Cypher was not present as a maternal mRNA and was absent during early development. Cypher mRNA was first detected at the 3-somite stage in adaxial somites, and as somites matured, cypher expression gradually enveloped the whole somite. Later, cypher expression was also found in the heart, in head and jaw musculature, and in the brain. We further identified 13 alternative spliced forms of cypher from zebrafish heart and skeletal muscle tissue, among them a very short form containing the PDZ domain but lacking the ZM (ZASP-like) motif and the LIM domains. Targeted gene knock-down experiments using cypher antisense morpholinos led to severe defects, including truncation of the embryo, deformation of somites, dilatation of the pericardium, and thinning of the ventricular wall. The phenotype could be rescued by a cypher form, which contains the PDZ domain and the ZM motif, but lacks all three LIM domains. These findings indicate that a PDZ domain protein is important for normal somite formation and in normal heart development. Treatment of zebrafish embryos with cyclopamine, which disrupts hedgehog signaling, abolished cypher expression in 9 somite and 15-somite stage embryos. Taken together, our data suggest that cypher may play a role downstream of sonic hedgehog, in a late stage of somite development, when slow muscle fibers differentiate and migrate from the adaxial cells.
- Subjects :
- medicine.medical_specialty
animal structures
Cyclopamine
Morpholino
Molecular Sequence Data
PDZ domain
Animals, Genetically Modified
chemistry.chemical_compound
Internal medicine
medicine
Animals
Amino Acid Sequence
Sonic hedgehog
Muscle, Skeletal
Zebrafish
Molecular Biology
LIM domain
Homeodomain Proteins
biology
Myocardium
Heart
Cell Biology
LIM Domain Proteins
Zebrafish Proteins
biology.organism_classification
Hedgehog signaling pathway
Protein Structure, Tertiary
Cell biology
Alternative Splicing
RNA, Messenger, Stored
Somite
medicine.anatomical_structure
Endocrinology
Somites
chemistry
Organ Specificity
embryonic structures
biology.protein
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 299
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....a1b663de3c2c7ba9ebac8ab0ac45b407
- Full Text :
- https://doi.org/10.1016/j.ydbio.2006.07.032