PUBLICATION
Zebrafish cypher is important for somite formation and heart development
- Authors
- van der Meer, D.L., Marques, I.J., Leito, J.T., Besser, J., Bakkers, J., Schoonheere, E., and Bagowski, C.P.
- ID
- ZDB-PUB-060921-23
- Date
- 2006
- Source
- Developmental Biology 299(2): 356-372 (Journal)
- Registered Authors
- Bagowski, Christoph P., Bakkers, Jeroen
- Keywords
- Cypher, Somites, ZASP, Z-line, PDZ, Myopathy, Heart development, LIM domain
- MeSH Terms
-
- Alternative Splicing
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Heart/embryology*
- Heart/physiology
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Molecular Sequence Data
- Muscle, Skeletal/embryology
- Muscle, Skeletal/metabolism
- Myocardium/metabolism
- Organ Specificity
- Protein Structure, Tertiary
- RNA, Messenger, Stored/metabolism
- Somites/physiology*
- Zebrafish/embryology*
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 16982050 Full text @ Dev. Biol.
Citation
van der Meer, D.L., Marques, I.J., Leito, J.T., Besser, J., Bakkers, J., Schoonheere, E., and Bagowski, C.P. (2006) Zebrafish cypher is important for somite formation and heart development. Developmental Biology. 299(2):356-372.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping