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

• Rachel E Shaw ^[3] ; Benjamin Kottler ^[4] ; Zoe N Ludlow ^[4] ; Edgar Buhl ^[1] ; Dongwook Kim ^[4] ; Sara Morais da Silva ^[2] ; Alina Miedzik ^[3] ; Antoine Coum ^[3] ; James JL Hodge ^[1] ; Frank Hirth ^[4] ; Rita Sousa‐Nunes ^[3]
  1. [1] University of Bristol

     University of Bristol

     Reino Unido

     
  2. [2] University of Cambridge

     University of Cambridge

     Cambridge District, Reino Unido

     
  3. [3] 1 Centre for Developmental Neurobiology Institute of Psychiatry, Psychology & Neuroscience King's College London London UK
  4. [4] 2 Department of Basic and Clinical Neuroscience Maurice Wohl Clinical Neuroscience Institute Institute of Psychiatry, Psychology & Neuroscience King's College London London UK

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 13, 2018, págs. 3-3
• Idioma: inglés
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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 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.