Imp and Syp RNA-binding proteins govern decommissioning ofDrosophilaneural stem cells

Abstract

The termination of the proliferation of Drosophila neural stem cells, also known as neuroblasts (NBs), requires a ‘decommissioning’ phase that is controlled in a lineage-specific manner. Most NBs, with the exception of those of the mushroom body (MB), are decommissioned by the ecdysone receptor and mediator complex, causing them to shrink during metamorphosis, followed by nuclear accumulation of Prospero and cell cycle exit. Here, we demonstrate that the levels of Imp and Syp RNA-binding proteins regulate NB decommissioning. Descending Imp and ascending Syp expression have been shown to regulate neuronal temporal fate. We show that Imp levels decline slower in the MB than in other central brain NBs. MB NBs continue to express Imp into pupation, and the presence of Imp prevents decommissioning partly by inhibiting the mediator complex. Late-larval induction of transgenic Imp prevents many non-MB NBs from decommissioning in early pupae. Moreover, the presence of abundant Syp in aged NBs permits Prospero accumulation that, in turn, promotes cell cycle exit. Together, our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages.

A single-cell transcriptomic atlas of the adultDrosophilaventral nerve cord

“…However, we 272 did not observe a striking physiological bias, as neither pros or Imp showed correlation 273 with fast-acting neurotransmitter markers (Figure 4-Figure supplement 2F). It has 274 previously been shown that pros labels late-born motor neurons from lineage 15B (Baek et 275 al., 2013), and that a trade-off of Imp and pros expression is essential for cell cycle exit of 276 post-embryonic type I neuroblasts in the VNC (Maurange et al, 2008;Yang et al, 2017). 277…”

Two distinct mechanisms silencechinmoinDrosophilaneuroblasts and neuroepithelial cells to limit their self-renewal

“…Important players in this post--transcriptional regulation could be the RBPs Imp, that could promote chinmo expression in early larval NBs, and Syncrip, that could repress chinmo in late larval NBs. Both RBPs indeed antagonistically regulate chinmo expression in mushroom body neurons and are respectively expressed in early and late NBs (Liu et al, 2015;Syed et al, 2017;Yang et al, 2017). In contrast, chinmo is mainly regulated at the transcriptional level in the NE of the optic lobe that expands during early larval development.…”

E93 Integrates Neuroblast Intrinsic State with Developmental Time to Terminate MB Neurogenesis via Autophagy

“…PI3K activity is nutrient regulated in many cell types, including MB neuroblasts [20], while in the salivary gland and fat body, increasing systemic ecdysone triggers reductions in levels of PI3K activity [21][22][23]. Two intrinsic neuroblast temporal factors, Imp (IGF-II, insulin growth factor, mRNA binding protein) and Syp (Syncrip), also regulate timing of MB neurogenesis termination [24,25]. When Imp is knocked down, MB neurogenesis terminates prematurely, and when Syp is knocked down, MB neurogenesis extends into adulthood [24,25].…”

“…Two intrinsic neuroblast temporal factors, Imp (IGF-II, insulin growth factor, mRNA binding protein) and Syp (Syncrip), also regulate timing of MB neurogenesis termination [24,25]. When Imp is knocked down, MB neurogenesis terminates prematurely, and when Syp is knocked down, MB neurogenesis extends into adulthood [24,25]. Imp and Syp, both RNAbinding proteins, are expressed in opposing temporal gradients in all neuroblasts, with Imp expressed at high levels first, followed by high Syp later [24][25][26][27].…”