BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo.
During left-right (L-R) axis formation, Nodal is expressed in the node and has a central role in the transfer of L-R information in the vertebrate embryo. Bone morphogenetic protein (BMP) signaling also has an important role for maintenance of gene expression around the node. Several members of the Cerberus/Dan family act on L-R patterning by regulating activity of the transforming growth factor-β (TGF-β) family. We demonstrate here that chicken Dan plays a critical role in L-R axis formation. Chicken Dan is expressed in the left side of the node shortly after left-handed Shh expression and before the appearance of asymmetrically expressed genes in the lateral plate mesoderm (LPM). In vitro experiments revealed that DAN inhibited BMP signaling but not NODAL signaling. SHH had a positive regulatory effect on Dan expression while BMP4 had a negative effect. Using overexpression and RNA interference-mediated knockdown strategies, we demonstrate that Dan is indispensable for Nodal expression in the LPM and for Lefty-1 expression in the notochord. In the perinodal region, expression of Dan and Nodal was independent of each other. Nodal up-regulation by DAN required NODAL signaling, suggesting that DAN might act synergistically with NODAL. Our data indicate that Dan plays an essential role in the establishment of the L-R axis by inhibiting BMP signaling around the node.
Division of Pattern Formation, Department of Organogenesis, Institute of Molecular Embryology and Genetics, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Kenjiro
K
Katsu
Daisuke
D
Tokumori
Norifumi
N
Tatsumi
Atsushi
A
Suzuki
Yuji
Y
Yokouchi
D000077582:Amisulpride; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D019521:Body Patterning / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism; D019556:COS Cells; D002642:Chick Embryo / Q000196:embryology / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004149:Dioxoles / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D055458:Left-Right Determination Factors / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008957:Models, Genetic; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D009672:Notochord / Q000196:embryology / Q000378:metabolism; D020897:Organizers, Embryonic / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013469:Sulpiride / Q000031:analogs & derivatives; D014981:Xenopus
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D030161:Avian Proteins; D001549:Benzamides; D055415:Bone Morphogenetic Protein 4; D004149:Dioxoles; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; C121419:caronte protein, Gallus gallus; D013469:Sulpiride; D000077582:Amisulpride