title: Asymmetric nodal signaling in the zebrafish diencephalon positions the pineal organ.
abstract: The vertebrate brain develops from a bilaterally symmetric neural tube but later displays profound anatomical and functional asymmetries. Despite considerable progress in deciphering mechanisms of visceral organ laterality, the genetic pathways regulating brain asymmetries are unknown. In zebrafish, genes implicated in laterality of the viscera (cyclops/nodal, antivin/lefty and pitx2) are coexpressed on the left side of the embryonic dorsal diencephalon, within a region corresponding to the presumptive epiphysis or pineal organ. Asymmetric gene expression in the brain requires an intact midline and Nodal-related factors. RNA-mediated rescue of mutants defective in Nodal signaling corrects tissue patterning at gastrulation, but fails to restore left-sided gene expression in the diencephalon. Such embryos develop into viable adults with seemingly normal brain morphology. However, the pineal organ, which typically emanates at a left-to-medial site from the dorsal diencephalic roof, becomes displaced in position. Thus, a conserved signaling pathway regulating visceral laterality also underlies an anatomical asymmetry of the zebrafish forebrain.
authors.affiliation: Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Liang
authors.forename: A
authors.initials: A
authors.lastname: Etheridge
authors.forename: L
authors.initials: L
authors.lastname: Hantsoo
authors.forename: A L
authors.initials: AL
authors.lastname: Rubinstein
authors.forename: S J
authors.initials: SJ
authors.lastname: Nowak
authors.forename: J C
authors.initials: JC
authors.lastname: Izpisúa Belmonte
authors.forename: M E
authors.initials: ME
authors.lastname: Halpern
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D001921:Brain / Q000196:embryology; D004027:Diencephalon / Q000196:embryology; D004707:Endoderm; D004838:Epiphyses; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D008297:Male; D016296:Mutagenesis; D055457:Nodal Protein; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D010870:Pineal Gland / Q000196:embryology*; D016548:Prosencephalon / Q000196:embryology; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D000097577:Homeobox Protein PITX2; C101485:homeobox protein PITX1; C433629:homeobox protein PITX3; C117508:lft1 protein, zebrafish; C512832:ndr2 protein, zebrafish; C110484:tdgf1 protein, zebrafish