Imp/Syp temporal gradients govern decommissioning ofDrosophilaneural stem cells

Abstract

Timing of Drosophila neuroblast decommissioning is controlled in a lineage-specific manner. Following a prepupal ecdysone pulse, the ecdysone receptor and mediator complex cause neuroblasts to shrink. Shrinking is followed by nuclear accumulation of Prospero and cell cycle exit. Only mushroom body (MB) neuroblasts escape early pupal termination. Here, we demonstrate that the opposing temporal gradients of Imp and Syp RNA-binding proteins that govern temporal fate also regulate neuroblast decommissioning. The Imp gradient declines slower in MB neuroblasts so they still express Imp when it is absent from others. The presence of Imp in MB neuroblasts prevents decommissioning partly through inhibiting the mediator complex. Moreover, a timely induction of Imp can protect many non-MB neuroblasts from aging. We also show that the increasing Syp gradient permits Prospero accumulation and neuroblast termination. Together our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages.

Delta-dependent Notch activation closes the early neuroblast temporal program to promote lineage progression and neurogenesis termination inDrosophila

“…Moreover, CB NBs that ectopically persisted tended to be larger than control CB NBs at early stages, consistent with the notion that cell size correlates with timing of termination (Fig. 3D,G) (Maurange et al, 2008;Siegrist et al, 2010;Homem et al, 2014;Yang et al, 2017). Next, although Serrate was not detected in CB NBs nor their GMC progeny, we still assayed CB NB number and size after Serrate knock down in both NBs and their GMC progeny (worGAL4,UAS-SerRNAi #HMS01179).…”

“…All central brain neuroblasts (CB NBs), except the MB NB subset (four per brain hemisphere) terminally differentiate or die during early pupal stages (Fig. 1A) (Truman and Bate, 1988;Ito and Hotta, 1992;Maurange et al, 2008;Siegrist et al, 2010;Homem et al, 2014;Yang et al, 2017). MB NBs divide several days longer and undergo apoptotic/autophagic cell death shortly before adult eclosion (Fig.…”

“…5A). Defects in intrinsic temporal factor expression lead to changes in the molecular composition of neuron types produced and defects in timing of CB NB elimination and neurogenesis termination (Isshiki et al, 2001;Maurange et al, 2008;Liu et al, 2015;Ren et al, 2017;Syed et al, 2017;Yang et al, 2017;Pahl et al, 2019). Because Notch signaling is required early to eliminate CB NBs, we assayed expression of early temporal factors, Cas and Svp.…”

Playing Well with Others: Extrinsic Cues Regulate Neural Progenitor Temporal Identity to Generate Neuronal Diversity

“…Ecdysone acts together with the Mediator complex and Syncrip to promote neuroblast size reduction, nuclear Prospero localization, and terminal differentiation [36, 58]. This late event also requires Hedgehog signaling [59], and down-regulation of Imp [60]. The detailed mechanism of ecdysone, Mediator, and Hedgehog signaling remains to be determined.…”

The making of the Drosophila mushroom body

“…Early-pupal elimination of non-MB NBs is initiated by ecdysone signaling and the mediator complex (Homem et al, 2014). Prolonged Imp expression in the MB-NBs (relative to other NBs) of early pupae protects them from this early elimination process by inhibiting components in the mediator complex (Yang et al, 2017). At 72 h APF, the MB-NBs start to decrease in size, followed by a reduction in mitotic activity 6 h later and, finally, termination at 96 h APF (Siegrist et al, 2010).…”