Semaphorin 2b Regulates Sleep-Circuit Formation in the Drosophila Central Brain

Xie, Xiaojun; Tabuchi, Masashi; Corver, Abel; Duan, Grace Y; Wu, Mark N.; Kolodkin, Alex L.

doi:10.1016/j.neuron.2019.07.019

Cited by 18 publications

(14 citation statements)

References 59 publications

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“…These cells invaded the CA, the peduncle, and ß and ß’ lobes as well as α and α’ lobes of the MB (Figure 5h, j–n). In contrast, we were not able to trace the neurons that invaded the fan‐shaped body, but according to their arborization pattern in the dFB, they must belong to tangential neurons that have cell bodies in the SLP, axonal arborizations in the 6th layer of the fan‐shaped body, and dendrites in the SMP (Donlea et al., 2018; Xie et al., 2019). These dFB neurons have been described by several previous studies due to their prominent role in sleep; they are revealed by the R23E10‐Gal4 driver (Donlea et al., 2014, 2018; Ni et al., 2019) and are also called ExFl2 neurons (Xie et al., 2019).…”

Section: Resultsmentioning

confidence: 98%

The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond

Reinhard

Bertolini

Saito

et al. 2022

J of Comparative Neurology

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Drosophila's lateral posterior neurons (LPNs) belong to a small group of circadian clock neurons that is so far not characterized in detail. Thanks to a new highly specific split-Gal4 line, here we describe LPNs' morphology in fine detail, their synaptic connections, daily bimodal expression of neuropeptides, and propose a putative role of this cluster in controlling daily activity and sleep patterns. We found that the three LPNs are heterogeneous. Two of the neurons with similar morphology arborize in the superior medial and lateral protocerebrum and most likely promote sleep. One unique, possibly wakefulness-promoting, neuron with wider arborizations extends from the superior lateral protocerebrum toward the anterior optic tubercle. Both LPN types exhibit manifold connections with the other circadian clock neurons, especially with those that control the flies' morning and evening activity (M-and E-neurons, respectively). In addition, they form synaptic connections with neurons of the mushroom bodies, the fanshaped body, and with many additional still unidentified neurons. We found that both LPN types rhythmically express three neuropeptides, Allostatin A, Allostatin C, and Diuretic Hormone 31 with maxima in the morning and the evening. The three LPN neuropeptides may, furthermore, signal to the insect hormonal center in the pars intercerebralis and contribute to rhythmic modulation of metabolism, feeding, and reproduction.We discuss our findings in the light of anatomical details gained by the recently published hemibrain of a single female fly on the electron microscopic level and of previous functional studies concerning the LPN.

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Section: Resultsmentioning

confidence: 98%

The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond

Reinhard

Bertolini

Saito

et al. 2022

J of Comparative Neurology

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“…Here, we have used temporally restricted genetic manipulations to show that inc acts during neuronal development to ultimately impact sleep in adulthood. While many genes are known to act in adults to impact sleep, developmental mechanisms underlying sleep regulation have only recently gained attention ( Chakravarti Dilley et al, 2020 ; Gong et al, 2021 ; Iwasaki et al, 2021 ; Xie et al, 2019 ). Our results underscore the importance of unbiased temporal genetic manipulations to define critical periods through which genes impact sleep, and suggest that genes may influence sleep through unappreciated developmental mechanisms.…”

Section: Discussionmentioning

confidence: 99%

insomniac links the development and function of a sleep-regulatory circuit

Jang

Lim

et al. 2021

eLife

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Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here we show that Insomniac (Inc), a conserved adaptor for the autism-associated Cul3 ubiquitin ligase, acts in a restricted period of neuronal development to impact sleep in adult Drosophila. The loss of inc causes structural and functional alterations within the mushroom body, a center for sensory integration, associative learning, and sleep regulation. In inc mutants, mushroom body neurons are produced in excess, develop anatomical defects that impede circuit assembly, and are unable to promote sleep when activated in adulthood. Our findings link neurogenesis and postmitotic development of sleep-regulatory neurons to their adult function and suggest that developmental perturbations of circuits that couple sensory inputs and sleep may underlie sleep dysfunction in neurodevelopmental disorders.

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“…Cell intrinsic biomechanical properties are essential for migrating cells to negotiate tight interstitial spaces while maintaining traction on substrate surfaces; in this context, balanced Plexin-B2 activity appeared to be crucial, as both Plexin-B2 deficiency or forced overexpression impeded GBM spread in intracranial transplants. This echoes the requirement for balanced levels of semaphorin/plexin activity during neurodevelopment, where both loss- and gain-of-function conditions can result in similar axon guidance defects 55 .…”

Section: Discussionmentioning

confidence: 62%

Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics

et al. 2021

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Infiltrative growth is a major cause of high lethality of malignant brain tumors such as glioblastoma (GBM). We show here that GBM cells upregulate guidance receptor Plexin-B2 to gain invasiveness. Deletion of Plexin-B2 in GBM stem cells limited tumor spread and shifted invasion paths from axon fiber tracts to perivascular routes. On a cellular level, Plexin-B2 adjusts cell adhesiveness, migratory responses to different matrix stiffness, and actomyosin dynamics, thus empowering GBM cells to leave stiff tumor bulk and infiltrate softer brain parenchyma. Correspondingly, gene signatures affected by Plexin-B2 were associated with locomotor regulation, matrix interactions, and cellular biomechanics. On a molecular level, the intracellular Ras-GAP domain contributed to Plexin-B2 function, while the signaling relationship with downstream effectors Rap1/2 appeared variable between GBM stem cell lines, reflecting intertumoral heterogeneity. Our studies establish Plexin-B2 as a modulator of cell biomechanics that is usurped by GBM cells to gain invasiveness.

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Semaphorin 2b Regulates Sleep-Circuit Formation in the Drosophila Central Brain

Cited by 18 publications

References 59 publications

The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond

The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond

insomniac links the development and function of a sleep-regulatory circuit

Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics

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