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Zebrafish Nkd1 promotes Dvl degradation and is required for left-right patterning
Journal article   Open access   Peer reviewed

Zebrafish Nkd1 promotes Dvl degradation and is required for left-right patterning

Igor Schneider, Patricia N Schneider, Sarah W Derry, Shengda Lin, Lacy J Barton, Trudi Westfall and Diane C Slusarski
Developmental biology, Vol.348(1), pp.22-33
12/01/2010
DOI: 10.1016/j.ydbio.2010.08.040
PMCID: PMC2976797
PMID: 20858476
url
https://doi.org/10.1016/j.ydbio.2010.08.040View
Published (Version of record) Open Access

Abstract

The establishment of the left-right (LR) axis in zebrafish embryos relies on signals from the dorsal forerunner cells (DFC) and the Kupffer's vesicle (KV). While the Wnt signaling network influences many aspects of embryonic development, its precise role in LR patterning is still unclear. One branch of the Wnt network leads to stabilization of β-catenin and activation of downstream target genes. Other Wnt ligands appear to act independently of β-catenin to modulate calcium release and influence cell polarity. Central to regulation of β-catenin and coordination of convergent extension (CE) movements is Dishevelled (Dvl). Naked Cuticle (Nkd) binds Dvl and modulates β-catenin-dependent and independent Wnt signaling. Here, we analyze the expression patterns of three zebrafish Nkd homologs and find enriched expression of nkd1 in DFCs and KV. Dvl is degraded upon Nkd1 overexpression in zebrafish. Knockdown of Nkd1 specifically in the DFC results in β-catenin nuclear localization and transcriptional activation as well as alterations to DFC migration, KV formation, ciliogenesis and LR patterning. Furthermore, we identify asymmetric expression of the Nodal antagonist charon around the KV and show that Nkd1 knockdown impacts asymmetric charon expression. Our findings show that Nkd1 acts as a β-catenin antagonist in the DFCs necessary for LR patterning.
Molecular Sequence Data Phosphoproteins - metabolism Zebrafish - embryology Gene Knockdown Techniques Gene Expression Regulation, Developmental Cilia - ultrastructure beta Catenin - physiology Protein Stability Dishevelled Proteins Carrier Proteins - physiology Zebrafish Proteins - biosynthesis Oligonucleotides, Antisense - pharmacology Animals, Genetically Modified Zebrafish - genetics Zebrafish Proteins - physiology Body Patterning - physiology Carrier Proteins - genetics Cell Movement - drug effects Zebrafish Proteins - deficiency Animals Zebrafish Proteins - isolation & purification Zebrafish - physiology Zebrafish Proteins - genetics Adaptor Proteins, Signal Transducing - metabolism Body Patterning - genetics

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