title: Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality.
abstract: The mechanisms that establish behavioral, cognitive, and neuroanatomical asymmetries are poorly understood. In this study, we analyze the events that regulate development of asymmetric nuclei in the dorsal forebrain. The unilateral parapineal organ has a bilateral origin, and some parapineal precursors migrate across the midline to form this left-sided nucleus. The parapineal subsequently innervates the left habenula, which derives from ventral epithalamic cells adjacent to the parapineal precursors. Ablation of cells in the left ventral epithalamus can reverse laterality in wild-type embryos and impose the direction of CNS asymmetry in embryos in which laterality is usually randomized. Unilateral modulation of Nodal activity by Lefty1 can also impose the direction of CNS laterality in embryos with bilateral expression of Nodal pathway genes. From these data, we propose that laterality is determined by a competitive interaction between the left and right epithalamus and that Nodal signaling biases the outcome of this competition.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom. mconcha@machi.med.uchile.cl
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Concha
authors.forename: Claire
authors.initials: C
authors.lastname: Russell
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Regan
authors.forename: Marcel
authors.initials: M
authors.lastname: Tawk
authors.forename: Samuel
authors.initials: S
authors.lastname: Sidi
authors.forename: Darren T
authors.initials: DT
authors.lastname: Gilmour
authors.forename: Marika
authors.initials: M
authors.lastname: Kapsimali
authors.forename: Lauro
authors.initials: L
authors.lastname: Sumoy
authors.forename: Kim
authors.initials: K
authors.lastname: Goldstone
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
authors.forename: David
authors.initials: D
authors.lastname: Kimelman
authors.forename: Teresa
authors.initials: T
authors.lastname: Nicolson
authors.forename: Stefan
authors.initials: S
authors.lastname: Gründer
authors.forename: Miranda
authors.initials: M
authors.lastname: Gomperts
authors.forename: Jonathan D W
authors.initials: JD
authors.lastname: Clarke
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D007839:Functional Laterality / Q000502:physiology*; D008969:Molecular Sequence Data; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D015027:Zebrafish