title: Xenopus nodal related-1 is indispensable only for left-right axis determination.
abstract: In Xenopus, multiple nodal-related genes are expressed in the organizer region. Among them, only Xenopus nodal related-1 (Xnr-1) is expressed unilaterally in the left lateral plate mesoderm (LPM) at late neurula-early tailbud stage. To elucidate the essential role of Xnr-1 for left-right specification, loss of function experiments using antisense morpholino oligonucleotides (MOs) targeting three different regions of Xnr-1 were performed. Left-side injection of Xnr-1 MO suppresses the left-side specific genes such as Xnr-1, Xenopus antivin (lefty) and Xenopus pitx2 and randomizes cardiac and visceral left-right orientation. In contrast, paraxial bilateral expression of Xnr-1 along the posterior notochord is not affected by the Xnr-1 MO. In embryos injected with the Xnr-1 MO, morphology of dorsal axial structures is normal and dorsal expression of sonic hedgehog and TGF-beta5 is not changed. Right-side injection of Nodal protein, or polyethyleneimine-based gene transfer of Xnr-1 mRNA in the right LPM induces Xnr-1 and pitx2 in the same side and fully (more than 90%) reverses situs of the internal organs. Left-side injection of Nodal protein restores normal left-right orientation in the embryos that were injected with Xnr-1 MO into the left blastomere and would cause randomization of the left-right axis without the Nodal injection. Taken together, unilateral expression of Xnr-1 in the left LPM directs the orientation of the left-right axis by driving the left-specific gene cascade. Knockdown of Xnr-1 function by the MOs suggests that Xnr-1 is indispensable only for the left-right orientation and dispensable for other embryonic axes probably owing to the redundancy in the function of multiple Xnrs.
authors.affiliation: Department of Biological Sciences, Kanagawa University, Hiratsuka, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Toyoizumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ogasawara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Kazue
authors.initials: K
authors.lastname: Mogi
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D055457:Nodal Protein; D020319:Oligodeoxyribonucleotides, Antisense / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins; D014982:Xenopus laevis; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D055457:Nodal Protein; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D000097577:Homeobox Protein PITX2; C512833:nodal1 protein, Xenopus