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

Research output: Contribution to journalArticlepeer-review

Rachel E Shaw, Benjamin Kottler, Zoe N Ludlow, Edgar Buhl, Dongwook Kim, Sara Morais da Silva, Alina Miedzik, Antoine Coum, James JL Hodge, Frank Hirth, Rita Sousa-Nunes

Original languageEnglish
Article numbere98163
Pages (from-to)1-16
Number of pages16
JournalThe EMBO journal
Volume37
Issue number13
Early online date4 May 2018
DOIs
Accepted/In press28 Mar 2018
E-pub ahead of print4 May 2018
Published2 Jul 2018

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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 Droso- phila. 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 match- ing 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.

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