title: Dvr1 transfers left-right asymmetric signals from Kupffer's vesicle to lateral plate mesoderm in zebrafish.
abstract: An early step in establishing left-right (LR) symmetry in zebrafish is the generation of asymmetric fluid flow by Kupffer's vesicle (KV). As a result of fluid flow, a signal is generated and propagated from the KV to the left lateral plate mesoderm, activating a transcriptional response of Nodal expression in the left lateral plate mesoderm (LPM). The mechanisms and molecules that aid in this transfer of information from the KV to the left LPM are still not clear. Here we provide several lines of evidence demonstrating a role for a member of the TGFβ family member, Dvr1, a zebrafish Vg1 ortholog. Dvr1 is expressed bilaterally between the KV and the LPM. Knockdown of Dvr1 by morpholino causes dramatically reduced or absent expression of southpaw (spaw, a Nodal homolog), in LPM, and corresponding loss of downstream Lefty (lft1 and lft) expression, and aberrant brain and heart LR patterning. Dvr1 morphant embryos have normal KV morphology and function, normal expression of southpaw (spaw) and charon (cha) in the peri-KV region and normal expression of a variety of LPM markers in LPM. Additionally, Dvr1 knockdown does not alter the capability of LPM to respond to signals that initiate and propagate spaw expression. Co-injection experiments in Xenopus and zebrafish indicate that Dvr1 and Spaw can enhance each other's ability to activate the Nodal response pathway and co-immunoprecipitation experiments reveal differential relationships among activators and inhibitors in this pathway. These results indicate that Dvr1 is responsible for enabling the transfer of a left-right signal from KV to the LPM.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah Molecular Medicine Program, Salt Lake City, UT 84112, USA.
authors.forename: Annita G
authors.initials: AG
authors.lastname: Peterson
authors.forename: Xinghao
authors.initials: X
authors.lastname: Wang
authors.forename: H Joseph
authors.initials: HJ
authors.lastname: Yost
mesh_terms: D000825:Animal Structures / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D002923:Cilia / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D047468:Immunoprecipitation; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D060172:Morpholinos / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C079678:Gdf3 protein, zebrafish; D060172:Morpholinos; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins
keywords: Axis formation; Cell signaling; Left–right; Nodal; Vg1; Zebrafish