Dicer is required for neural stem cell multipotency and lineage progression during cerebral cortex development

Research output: Contribution to journalJournal articleResearchpeer-review

Background: During cerebral cortex development, multipotent neural progenitor cells generate a variety of neuronal subtypes in a fixed temporal order. How a single neural progenitor cell generates the diversity of cortical projection neurons in a temporal sequence is not well understood. Based on their function in developmental timing in other systems, Dicer and microRNAs are potential candidate regulators of cellular pathways that control lineage progression in neural systems.Results: Cortex-specific deletion of Dicer results in a marked reduction in the cellular complexity of the cortex, due to a pronounced narrowing in the range of neuronal types generated by Dicer-null cortical stem and progenitor cells. Instead of generating different classes of lamina-specific neurons in order over the 6-day period of neurogenesis, Dicer null cortical stem and progenitor cells continually produce one class of deep layer projection neuron. However, gliogenesis in the Dicer-null cerebral cortex was not delayed, despite the loss of multipotency and the failure of neuronal lineage progression.Conclusions: We conclude that Dicer is required for regulating cortical stem cell multipotency with respect to neuronal diversity, without affecting the larger scale switch from neurogenesis to gliogenesis. The differences in phenotypes reported from different timings of Dicer deletion indicate that the molecular pathways regulating developmental transitions are notably dosage sensitive.

Original languageEnglish
Article number14
JournalNeural Development
Volume8
Issue number1
ISSN1749-8104
DOIs
Publication statusPublished - 29 Jul 2013
Externally publishedYes

Bibliographical note

Funding Information:
We thank Alexander Tarakhovsky for generously providing the Dicer mice and the members of the Livesey lab for constructive feedback on this study. NS is supported by the Woolf-Fisher Trust (NZ). TA is supported by the Wenner-Gren Foundations. This research was supported by grant funding to FJL from the Wellcome Trust. Research in the FJL lab benefits from core support to the Gurdon Institute from the Wellcome Trust and Cancer Research UK.

    Research areas

  • Cerebral cortex, Dicer, microRNA, Multipotency, Stem cells

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