A new proof-of-principle study from the CDN demonstrates a means to expand specific neural lineages, the neurons/glia produced from a single stem cell, in vivo in a non-tumorigenic way. Previous studies have shown that the transcription factor Prospero mediates differentiation in Drosophila neural lineages. However, and counter intuitively, the researchers found that by lowering Prospero levels, they could induce amplification of neuronal number as well as of neural progenitors. With the lineage resolution uniquely offered by this model, they show that extra neurons produced obey lineage-specific patterning, physiological properties and neurotransmitter profile. Targeted to identified neural lineages, this in vivo expansion mechanism amplified GABAergic interneurons of the central complex in the adult fly brain.
Remarkably, extra neurons were able to integrate functionally into the lineage-related microcircuit analysed and this circuit functioned well-enough with the extra cells (seen by motor behavioural experiments). This showed that this circuit is plastic at the level of cell numbers, i.e., able to accommodate a range of neuronal numbers. These findings support the hypothesis that clonal expansion of an entire circuit module is a mechanism of brain evolution. The findings are reported in the EMBO Journal.
This work was supported by grants from the Wellcome Trust Grant 107414/Z/15/Z (to S.M.d.S.); the UK Biotechnology and Biological Sciences Research Council Grant BB/J017221/1 (to J.J.L.H.); UK Medical Research Council (G070149; MR/L010666/1), the UK Biotechnology and Biological Sciences Research Council (BB/N001230/1), the Royal Society (Hirth2007/R2) (to F.H.); Cancer Research UK Career Development Fellowship and Royal Society (RG2016/R1) (to R.S.N.).
Paper reference: 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. In vivo expansion of functionally integrated GABAergic interneurons by targeted increase in neural progenitors. EMBO Journal (4 May 2018). DOI 10.15252/embj.201798163