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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.
Original languageEnglish
Article numbere98163
Pages (from-to)1-16
Number of pages16
JournalThe EMBO journal
Issue number13
Early online date4 May 2018
Publication statusPublished - 2 Jul 2018


  • circuit plasticity; evolutionary neurobiology; lineage expansion; neural stem cells; Prospero


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