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

Pahl, Matthew C; Doyle, Susan E.; Siegrist, Sarah E.

doi:10.1016/j.cub.2019.01.039

Cited by 54 publications

(57 citation statements)

References 68 publications

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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%

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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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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“…The mushroom body neuroblasts keep proliferating until late metamorphosis, when they undergo apoptosis 12 . By late metamorphosis, the Drosophila pupal brain is normally completely non-cycling and negative for markers of proliferation such as thymidine analog incorporation and mitotic markers [13][14][15] In the adult, very little neurogenesis and gliogenesis are normally observed 12,13,16 . A population of about 40 adult neural progenitors has been reported in the optic lobe and a population of glial progenitors has been reported in the central brain 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Polyploidy in the adultDrosophilabrain

Nandakumar

Grushko

Buttitta

2019

Preprint

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Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal's lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the ageing adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid with age in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region with age. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in ageing Drosophila melanogaster brains. for providing fly stocks, particularly the labs of Cheng-

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

Cited by 54 publications

References 68 publications

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

Polyploidy in the adultDrosophilabrain

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

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