Retinal homeobox promotes cell growth, proliferation and survival of mushroom body neuroblasts in the Drosophila brain

Kraft, Karoline F.; Massey, Eva M.; Kolb, Dieter M.; Walldorf, Uwe; Urbach, Rolf

doi:10.1016/j.mod.2016.07.003

Cited by 24 publications

(35 citation statements)

References 83 publications

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“…This is consistent with normal ending of MB NBs by apoptosis rather than through Syp-dependent, Pros-mediated cell cycle exit ( Siegrist et al, 2010 ). Insulin signaling and the transcription factor Retinal homeobox are known to promote MB NB proliferation and survival ( Kraft et al, 2016 ; Lin et al, 2013 ; Siegrist et al, 2010 ). Although endogenous Imp protects MB NBs from shrinking in early pupae through inhibiting the mediator complex, it is unclear how ectopic Imp can extend MB NBs into adults that might involve different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…The adult Drosophila central brain is built from ~100 neuroblasts (Lee et al, 2020;Urbach and Technau, 2004;Wong et al, 2013;Yu et al, 2013a) that divide continuously from L1 to L3 (Homem et al, 2014;Sousa-Nunes et al, 2010;Yang et al, 2017). Each asymmetric division regenerates the neuroblast and produces an intermediate progenitor called ganglion mother cell (GMC) that divides only once, typically producing two different cell types (Lin et al, 2010;Spana and Doe, 1996;Truman et al, 4 continuously (unlike any other neuroblast) from the late embryonic stages until the end of pupation (~9 days for ~250 divisions each) ( Figure 1A) (Ito et al, 1997;Kraft et al, 2016;Kunz et al, 2012;Kurusu et al, 2009;Pahl et al, 2019;Siegrist et al, 2010;Sipe and Siegrist, 2017). Furthermore, the two neurons born from each mushroom body GMC are identical.…”

Section: Introductionmentioning

confidence: 99%

“…To produce this very large number of neurons, mushroom body development is unique in many respects. Mushroom body neurons are born from four identical neuroblasts that divide continuously (unlike any other neuroblast) from the late embryonic stages until the end of pupation (~9 days for ~250 divisions each) ( Figure 1A ; Ito et al, 1997 ; Kraft et al, 2016 ; Kunz et al, 2012 ; Kurusu et al, 2009 ; Lee et al, 1999 ; Pahl et al, 2019 ; Siegrist et al, 2010 ; Sipe and Siegrist, 2017 ). Furthermore, the two neurons born from each mushroom body GMC are identical.…”

Section: Introductionmentioning

confidence: 99%

Extrinsic activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

Rossi

Desplan

2020

eLife

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Temporal patterning of neural progenitors leads to the sequential production of diverse neuronal types. To better understand how extrinsic cues interact with intrinsic temporal programs to contribute to temporal patterning, we studied the Drosophila mushroom body neural progenitors (neuroblasts). Each of these four neuroblasts divides ~250 times to sequentially produce only three main neuronal types over the course of ~9 days of development: g, followed by α'β', and finally αβ neurons. The intrinsic temporal clock is composed of two RNA-binding proteins, IGF-II mRNA binding protein (Imp) and Syncrip (Syp), that are expressed in opposing temporal gradients. Activin signaling affects the production of α'β' neurons but whether and how this extrinsic cue interacts with the intrinsic temporal program was not known. We show that the Activin ligand Myoglianin produced from glia downregulates the levels of the intrinsic temporal factor Imp in mushroom body neuroblasts. In neuroblasts mutant for the Activin signaling receptor baboon, Imp levels are higher than normal during the α'β' temporal window, leading to the specific loss of the α'β' neurons. The intrinsic temporal clock still progresses but with a delay, skipping the α'β' window without affecting the total number of neurons produced: The number of g neurons likely increases, α'β' disappear, and the number of αβ neurons decreases. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.

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“…Mushroom body neurons (Kenyon cells) are extensively studied for their roles in learning and memory (Cognigni et al, 2018). They are born from four identical neuroblasts per hemisphere, which divide continuously from the late embryonic stages until the end of pupation (~9 days for ~250 divisions each) ( Figure 1A) (Ito et al, 1997;Kraft et al, 2016;Kurusu et al, 2009;Pahl et al, 2019;Siegrist et al, 2010;Sipe and Siegrist, 2017). Within this very long period, only three main neuronal types are produced sequentially, first g, followed by a'b', and then ab ( Figure 1A), representing the simplest lineage in the central brain.…”

Section: Introductionmentioning

confidence: 99%

Extrinsic Activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

Rossi

Desplan

2019

Preprint

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How diverse neuronal types are sequentially generated from individual neural stem cells is a central question in neurobiology. This "temporal patterning" is controlled by both intrinsic and extrinsic cues. Whether and how extrinsic cues interact with intrinsic programs to increase neuronal diversity, or if they only fine-tune the timing of temporal transitions, is not known. We use the simple Drosophila mushroom body lineage, comprised of only three neuronal types that are sequentially produced, to address the role of extrinsic cues in temporal patterning. As they age, mushroom body stem cells (neuroblasts) advance through intrinsic and opposing temporal gradients of two RNA-binding proteins, Imp and Syp. These intrinsic gradients are used to first produce g, then a'b', and finally ab neurons. The specification of each neuronal type is temporally confined to specific developing stages, and progression from one temporal window to the next occurs concurrently with key, developmental events. This suggests that extrinsic cues play important roles in patterning temporal identity in this lineage. We show that an extrinsic cue, Activin, not only times the young (Imp) to old (Syp) neuroblast fate transition but that it is also essential for increasing neuronal diversity by defining the mid-temporal window (a'b'). Activin reduces the levels of the intrinsic factor Imp, creating a scenario where Imp and Syp are both at low levels for an extended period. In Activin receptor mutants, a'b' neurons are not generated because high Imp levels inhibit the activation of a'b' effectors, including ecdysone receptor signaling.Additionally, the g temporal window appears to be extended and the ab window is shortened, due to a delayed Imp to Syp transition. Our results illustrate that temporal extrinsic cues during neurogenesis can modify an intrinsic temporal program to increase neuronal diversity.

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Retinal homeobox promotes cell growth, proliferation and survival of mushroom body neuroblasts in the Drosophila brain

Cited by 24 publications

References 83 publications

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

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

Extrinsic activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

Extrinsic Activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

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