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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)
255 Downloads (Pure)


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.

Original languageEnglish
Article numbere98163
Number of pages16
JournalEMBO Journal
Issue number12
Early online date4 May 2018
Publication statusPublished - 15 Jun 2018


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


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