Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality

Miguel L. Concha, Claire Russell, Jennifer C. Regan, Marcel Tawk, Samuel Sidi, Darren T. Gilmour, Marika Kapsimali, Lauro Sumoy, Kim Goldstone, Enrique Amaya, David Kimelman, Teresa Nicolson, Stefan Gründer, Miranda Gomperts, Jonathan D.W. Clarke, Stephen W. Wilson

Research output: Contribution to journalArticle

121 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)423-438
Number of pages16
JournalNeuron
Volume39
Issue number3
DOIs
StatePublished - Jul 31 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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    Concha, M. L., Russell, C., Regan, J. C., Tawk, M., Sidi, S., Gilmour, D. T., Kapsimali, M., Sumoy, L., Goldstone, K., Amaya, E., Kimelman, D., Nicolson, T., Gründer, S., Gomperts, M., Clarke, J. D. W., & Wilson, S. W. (2003). Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. Neuron, 39(3), 423-438. https://doi.org/10.1016/S0896-6273(03)00437-9