Local tissue interactions across the dorsal midline of the forebrain

establish CNS laterality

Concha, M.L., Russell, C., Regan, J.C., Tawk1, 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. and Wilson, S.W.

Neuron 39:423-438 (2003) (Full Article, 1700K)

Abstract

Animals show behavioural, cognitive and neuroanatomical asymmetries but the

mechanisms that establish these asymmetries are not well understood. In this study, we

analyse the morphogenetic events, tissue interactions and signals that regulate the

development of asymmetric nuclei in the epithalamic region of the dorsal forebrain. We

show that the unilateral parapineal organ has a bilateral origin and that some parapineal

precursors migrate across the midline to form this left-sided nucleus. The parapineal

subsequently innervates the left habenular nucleus, which itself derives from ventral

epithalamic cells directly adjacent to the parapineal precursors. We show that ablation of

cells in the left ventral epithalamus can lead to reversal of epithalamic laterality in wild

type embryos and can impose the direction of CNS asymmetry in embryos in which

laterality is normally randomised. These data lead us to propose that laterality is

determined by a competitive interaction between the left and the right epithalamus. We

suggest that the role of Nodal signalling is to bias the outcome of this competition. In

support of this, we show that in embryos with bilateral expression of Nodal pathway

genes, unilateral modulation of Nodal activity by Lefty1 can impose the direction of CNS

laterality.

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