Abstract
Gpr161 (also known as RE2) is an orphan G protein-coupled receptor (GPCR) that is expressed during embryonic development in zebrafish. Determining its biological function has proven difficult due to lack of knowledge regarding its natural or synthetic ligands. Here, we show that targeted knockdown of gpr161 disrupts asymmetric gene expression in the lateral plate mesoderm, resulting in aberrant looping of the heart tube. This is associated with elevated Ca(2+) levels in cells lining the Kupffer's vesicle and normalization of Ca(2+) levels, by over-expression of ncx1 or pmca-RNA, is able to partially rescue the cardiac looping defect in gpr161 knockdown embryos. Taken together, these data support a model in which gpr161 plays an essential role in left-right (L-R) patterning by modulating Ca(2+) levels in the cells surrounding the Kupffer's vesicle.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Body Patterning / genetics
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Body Patterning / physiology*
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Calcium / metabolism
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Calcium Signaling
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Embryo, Nonmammalian / metabolism
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Embryo, Nonmammalian / physiology
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Gene Expression Regulation, Developmental
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In Situ Hybridization
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Models, Biological
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Molecular Sequence Data
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Oligonucleotides, Antisense / pharmacology
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Protein Structure, Tertiary
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Receptors, G-Protein-Coupled / physiology*
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Sequence Homology, Amino Acid
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Zebrafish / embryology
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Zebrafish / genetics
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Zebrafish / metabolism
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Zebrafish Proteins / antagonists & inhibitors
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
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Zebrafish Proteins / physiology*
Substances
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GPR161 protein, mouse
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Oligonucleotides, Antisense
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Receptors, G-Protein-Coupled
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Zebrafish Proteins
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Calcium