期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 31, 页码 10911-10926出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0601-15.2015
关键词
mRNA translation; neocortex; ribosome; thalamocortical; Wnt
资金
- National Institutes of Health (NIH) [NS064303, NS075367]
- Robert Wood Johnson Medical School (RWJMS)
- NIH [1RC1CA147187, R21DA032984, R21DA035594, GM067005]
- Kirschstein National Research Service Award F30 NIH Fellowship [1F30MH106220-01]
- National Science Foundation Integrative Graduate Education and Research Traineeship Program Fellowship [DGE0801620]
Neocortical development requires tightly controlled spatiotemporal gene expression. However, the mechanisms regulating ribosomal complexes and the timed specificity of neocortical mRNA translation are poorly understood. We show that active mRNA translation complexes (polysomes) contain ribosomal protein subsets that undergo dynamic spatiotemporal rearrangements during mouse neocortical development. Ribosomal protein specificity within polysome complexes is regulated by the arrival of in-growing thalamic axons, which secrete the morphogen Wingless-related MMTV (mouse mammary tumor virus) integration site 3 (WNT3). Thalamic WNT3 release during midneurogenesis promotes a change in the levels of Ribosomal protein L7 in polysomes, thereby regulating neocortical translation machinery specificity. Furthermore, we present an RNA sequencing dataset analyzing mRNAs that dynamically associate with polysome complexes as neocortical development progresses, and thus may be regulated spatiotemporally at the level of translation. Thalamic WNT3 regulates neocortical translation of two such mRNAs, Foxp2 and Apc, to promote FOXP2 expression while inhibiting APC expression, thereby driving neocortical neuronal differentiation and suppressing oligodendrocyte maturation, respectively. This mechanism may enable targeted and rapid spatiotemporal control of ribosome composition and selective mRNA translation in complex developing systems like the neocortex.
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