Inositol polyphosphates regulate zebrafish left-right asymmetry.
Vertebrate body plans have a conserved left-right (LR) asymmetry manifested in the position and anatomy of the heart, visceral organs, and brain. Recent studies have suggested that LR asymmetry is established by asymmetric Ca2+ signaling resulting from cilia-driven flow of extracellular fluid across the node. We report here that inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1), which generates inositol hexakisphosphate, is critical for normal LR axis determination in zebrafish. Zebrafish embryos express ipk1 symmetrically during gastrulation and early segmentation. ipk1 knockdown by antisense morpholino oligonucleotide injection randomized LR-specific gene expression and organ placement, effects that were associated with reduced intracellular Ca2+ flux in cells surrounding the ciliated Kupffer's vesicle, a structure analogous to the mouse node. Our data suggest that the pathway for inositol hexakisphosphate production is a key regulator of asymmetric Ca(2+) flux during LR specification.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21(st) Avenue South, Nashville, Tennessee 37232, USA.
Bhaskarjyoti
B
Sarmah
Andrew J
AJ
Latimer
Bruce
B
Appel
Susan R
SR
Wente
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D020013:Calcium Signaling; D004625:Embryo, Nonmammalian / Q000378:metabolism; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D010833:Phytic Acid / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D029961:Zebrafish Proteins; D010833:Phytic Acid; D017853:Phosphotransferases (Alcohol Group Acceptor); C503314:ippk protein, zebrafish