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

TY - JOUR

T1 - In vivo expansion of functionally integrated GABAergic interneurons by targeted increase in neural progenitors

AU - Shaw, Rachel E

AU - Kottler, Benjamin

AU - Ludlow, Zoe N

AU - Buhl, Edgar

AU - Kim, Dongwook

AU - Morais da Silva, Sara

AU - Miedzik, Alina

AU - Coum, Antoine

AU - Hodge, James JL

AU - Hirth, Frank

AU - Sousa-Nunes, Rita

N1 - © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2018/7/2

Y1 - 2018/7/2

N2 - 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.

AB - 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.

KW - circuit plasticity; evolutionary neurobiology; lineage expansion; neural stem cells; Prospero

U2 - 10.15252/embj.201798163

DO - 10.15252/embj.201798163

M3 - Article

C2 - 29728368

SN - 0261-4189

VL - 37

SP - 1

EP - 16

JO - The EMBO journal

JF - The EMBO journal

IS - 13

M1 - e98163

ER -