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In vivo expansion of functionally integrated GABAergic interneurons by targeted increase of neural progenitors

Research output: Contribution to journalArticle

Original languageEnglish
Article numbere98163
Number of pages16
JournalEMBO Journal
Volume37
Issue number12
Early online date4 May 2018
DOIs
DateAccepted/In press - 15 Feb 2018
DateE-pub ahead of print - 4 May 2018
DatePublished (current) - 15 Jun 2018

Abstract

A central hypothesis for brain evolution is that it might occur via expansion of progenitor cells and subsequent lineage-dependent formation of neural circuits. Here, we report in vivo amplification and functional integration of lineage-specific circuitry in Drosophila. Levels of the cell fate determinant Prospero were attenuated in specific brain lineages within a range that expanded not only progenitors but also neuronal progeny, without tumor formation. Resulting supernumerary neural stem cells underwent normal functional transitions, progressed through the temporal patterning cascade, and generated progeny with molecular signatures matching source lineages. Fully differentiated supernumerary gamma-amino butyric acid (GABA)-ergic interneurons formed functional connections in the central complex of the adult brain, as revealed by in vivo calcium imaging and open-field behavioral analysis. Our results show that quantitative control of a single transcription factor is sufficient to tune neuron numbers and clonal circuitry, and provide molecular insight into a likely mechanism of brain evolution.

    Research areas

  • Neural stem cells , Prospero , lineage expansion , circuit plasticity , evolutionary neurobiology

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via EMBOpress at https://doi.org/10.15252/embj.201798163 . Please refer to any applicable terms of use of the publisher.

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