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| Open AccessThe AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
Mitochondria emerged as essential actors of neural circuits development. Here, the authors uncovered that the AMPK-related kinase NUAK1 controls axonal mitochondrial metabolism through the regulation of the mitochondrial microprotein BRAWNIN.
- Marine Lanfranchi
- , Sozerko Yandiev
- & Julien Courchet
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| Open AccessNeonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment
Neonatal brain dynamics are not well understood. Here, the authors characterise brain transient states in neonates, and show that preterm infants display altered whole brain dynamics and an atypical repertoire of regional transient states, which are associated with behavioural outcomes at 18 months of age.
- Lucas G. S. França
- , Judit Ciarrusta
- & Dafnis Batalle
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| Open AccessKDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors
Zhang et al. report that KDM2B-∆CxxC activated Wnt signaling in the developing hippocampi, where the migration and differentiation of neural progenitors were blocked. KDM2B-∆CxxC mice exhibited defects of hippocampal morphology and related behaviors.
- Bo Zhang
- , Chen Zhao
- & Yan Zhou
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| Open AccessCelf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex
While progress in early human cortical development is acknowledged, a limited understanding persists regarding transcriptomic and translational profiles in subplate neurons. Here, the authors discovered an enrichment of autism spectrum disorder risk genes in subplate neurons, underscoring the crucial role played by the RNA-binding protein CELF4 in translating synaptic mRNAs during neocortical development.
- Iva Salamon
- , Yongkyu Park
- & Mladen-Roko Rasin
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| Open AccessRetina-derived signals control pace of neurogenesis in visual brain areas but not circuit assembly
How does sensory input shape cellular composition and circuit structure of the brain during development? This study shows that, without connections to the retina, neurons in visual brain areas differentiate and wire up normally, albeit more slowly.
- Shachar Sherman
- , Irene Arnold-Ammer
- & Herwig Baier
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| Open AccessNon-uniform temporal scaling of developmental processes in the mammalian cortex
Marsupial mammals take much longer to develop than similarly sized placental mammals, though how brain development occurs across these different periods is unclear. Here they show that the neurodevelopmental events of cortical neurogenesis, cell migration and axon extension do not all temporally scale to the same extent.
- Annalisa Paolino
- , Elizabeth H. Haines
- & Laura R. Fenlon
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Article
| Open AccessElevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway
MAP1B is bound and regulated by fragile X protein FMRP. Here, the authors show that elevated levels of MAP1B reduce the morphological and physiological maturation of human neurons and impair social behavior in mice.
- Yu Guo
- , Minjie Shen
- & Xinyu Zhao
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| Open AccessAnatomical and functional maturation of the mid-gestation human enteric nervous system
Dershowitz and colleagues assess second trimester human fetal enteric nervous system development and function. They describe structural reorganization of the enteric nervous system that corresponds to gastrointestinal motility onset in ex vivo preparations.
- Lori B. Dershowitz
- , Li Li
- & Julia A. Kaltschmidt
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Article
| Open AccessAn entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis
Entosis is a process of cell cannibalism observed in cancer. Here, Sterling and colleagues report that entosis can also play a role in brain development and can contribute to the pathogenesis of microcephaly.
- Noelle A. Sterling
- , Jun Young Park
- & Seonhee Kim
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Article
| Open AccessFunction of bidirectional sensitivity in the otolith organs established by transcription factor Emx2
The inner ear is highly organized, with distinct domains being located across the Line of Polarity Reversal (LPR). Here they show that Emx2 establishes the LPR and bidirectional selectivity of otolith organs, and that loss of the LPR in mice affects swimming and balance.
- Young Rae Ji
- , Yosuke Tona
- & Doris K. Wu
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| Open AccessTranscriptional dynamics of murine motor neuron maturation in vivo and in vitro
Patel et al. show that gene expression and regulation in motor neurons is dynamic until juvenile age. A core subprogram (~40% of genes) is faithfully recapitulated in cultured motor neurons, with neuronal activity playing only a modulatory role.
- Tulsi Patel
- , Jennifer Hammelman
- & Hynek Wichterle
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| Open AccessPregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice
During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.
- Steven Schepanski
- , Mattia Chini
- & Petra C. Arck
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| Open AccessAn epigenome atlas of neural progenitors within the embryonic mouse forebrain
The authors took a multimodal approach to characterize the differential transcriptome and epigenetic landscape between distinct regions of the embryonic mouse forebrain, revealing many unexplored presumptive promoter-enhancer interactions.
- Christopher T. Rhodes
- , Joyce J. Thompson
- & Timothy J. Petros
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| Open AccessComparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human
The evolution of epigenetic regulation of brain development in primates is not well understood. Here, the authors perform a comparative study of epigenetic dynamics of early prefrontal cortex development between human and rhesus macaque, finding divergent regulatory elements that may be related to cognitive capacity.
- Xuelong Yao
- , Zongyang Lu
- & Jiang Liu
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| Open AccessDissociable multi-scale patterns of development in personalized brain networks
Studies of brain network development typically focus on a single scale. Here, the authors derived personalized functional networks across scales, and find that network development systematically adheres to and strengthens hierarchical cortical organization.
- Adam R. Pines
- , Bart Larsen
- & Theodore D. Satterthwaite
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| Open AccessImpaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior
Early postnatal interruption of the bidirectional GABA/TNFSF12 signaling between parvalbumin-positive interneurons and oligodendrocyte precursor cells impairs correct prefrontal cortical network activity and social cognitive behavior later in life.
- Li-Pao Fang
- , Na Zhao
- & Xianshu Bai
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| Open AccessThe histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development
Neural cell type diversification during development is a complex and highly regulated process. Here, the authors show that the histone H3-lysine 27 demethylase Kdm6b promotes and inhibits the generation of specific motor neuron subtypes during the development of the mouse spinal cord.
- Wenxian Wang
- , Hyeyoung Cho
- & Soo-Kyung Lee
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| Open AccessTemporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling
Long-range looping of an enhancer to a promoter (E-P looping) is a key feature of gene activation; thus, regulation of E-P looping could serve as an effective strategy to precisely control gene expression. Here the authors propose the Drosophila chromatin insulator antagonist Shep represses expression of genes during neuronal maturation by preventing E-P looping.
- Dahong Chen
- , Catherine E. McManus
- & Elissa P. Lei
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Article
| Open AccessBrain adiponectin signaling controls peripheral insulin response in Drosophila
Circulating adiponectin controls sensitivity to insulin in tissues. Here, Arquier et al. show that adiponectin receptor activity in neurons of the Drosophila brain controls insulin response in peripheral tissues via juvenile hormone signaling.
- Nathalie Arquier
- , Marianne Bjordal
- & Pierre Léopold
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| Open AccessA generative network model of neurodevelopmental diversity in structural brain organization
The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.
- Danyal Akarca
- , Petra E. Vértes
- & Duncan E. Astle
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| Open AccessFoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes
Cortical excitatory/inhibitory (E/I) imbalance is a feature of autism spectrum disorder (ASD). Here, the authors show that FoxG1 regulates the formation of cortical GABAergic circuits affecting social behaviour during a specific postnatal time window in mouse models of ASD.
- Goichi Miyoshi
- , Yoshifumi Ueta
- & Mariko Miyata
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| Open AccessTanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons
Alterations of the mTOR signalling pathway are associated with neurodevelopmental defects. Regulators of the mTOR kinase activity are not fully described. Here, the authors show that Tanc2, a scaffolding protein, acts as a direct inhibitor of mTOR kinase activity in the developing mouse brain and cultured human neurons.
- Sun-Gyun Kim
- , Suho Lee
- & Eunjoon Kim
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Article
| Open AccessA conserved role for the ALS-linked splicing factor SFPQ in repression of pathogenic cryptic last exons
SFPQ is a splicing factor and its mutations are associated to amyotrophic lateral sclerosis (ALS) patients. Here, the authors show that SFPQ represses the use of pathogenic cryptic last exons in zebrafish, mouse and human cells.
- Patricia M. Gordon
- , Fursham Hamid
- & Corinne Houart
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| Open AccessAxonal chemokine-like Orion induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling
Astrocytes can engulf axonal debris in the developing brain. However, the mechanisms regulating astrocyte recruitment to the proper axons is unclear. Here, the authors identify Orion as a signal for astrocyte infiltration and engulfment to the mushroom bodies in the Drosophila developing brain.
- Ana Boulanger
- , Camille Thinat
- & Jean-Maurice Dura
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| Open AccessHost interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex
Transplantation of embryonic interneurons can restore juvenile plasticity to the adult host visual cortex. Here, the authors show that transplanted embryonic interneurons reactivate cortical plasticity via Neuregulin/ErbB4 signaling in host parvalbumin interneurons.
- XiaoTing Zheng
- , Kirstie J. Salinas
- & Sunil P. Gandhi
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| Open AccessThe histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus
Mutations in the MLL4 gene can cause Kabuki syndrome, whose underlying molecular mechanisms are unclear. Here, the authors show that Mll4 epigenetically regulates the transcriptional program leading to the formation of GHRH-neurons in the developing mouse hypothalamus.
- Christian Huisman
- , Young A. Kim
- & Jae W. Lee
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| Open AccessPrimary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus
Ciliary defects and obesity has been associated, but the underlying mechanism is unclear. Here, the authors show that inhibition of ciliogenesis in POMC neurons during development results in lysosomal protein degradation-dependent axonal disruption and adult obesity in mice.
- Chan Hee Lee
- , Do Kyeong Song
- & Min-Seon Kim
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| Open AccessBrainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease
Krabbe disease is caused by GALC deficiency, leading to accumulation of cytotoxic psychosine, demyelination, and neurodegeneration. Here, the authors develop a Galc flox mouse line to model Krabbe disease and unveil that early postnatal GALC neuronal expression is critical for disease pathogenesis.
- Nadav I. Weinstock
- , Conlan Kreher
- & Daesung Shin
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| Open AccessSurfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity
Cell surface proteins contribute to neuronal development and activity-dependent synaptic plasticity. Here, the authors perform a time-resolved surfaceome analysis of developing primary neurons and in response to homeostatic synaptic scaling and chemical long-term potentiation (cLTP), revealing surface proteome remodeling largely independent of global proteostasis.
- Marc van Oostrum
- , Benjamin Campbell
- & Bernd Wollscheid
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Article
| Open AccessSymmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80
Chromatin mediates transcription and DNA repair. Here, the authors show distinct roles of chromatin remodeler INO80 in expression of YY1-regulated genes and repair of DNA breaks by homologous recombination, a DNA repair pathway important for symmetrically-dividing neural progenitors.
- Jason M. Keil
- , Daniel Z. Doyle
- & Kenneth Y. Kwan
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Article
| Open AccessComprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease
Here the authors present an approach that can reveal the full complement of mRNA isoforms encoded by individual genes, and they identify a major isoform of the retinal degeneration gene CRB1 which functions at the cell-cell junctions of the outer limiting membrane to promote photoreceptor survival.
- Thomas A. Ray
- , Kelly Cochran
- & Jeremy N. Kay
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Article
| Open AccessNolz1 expression is required in dopaminergic axon guidance and striatal innervation
The mechanisms regulating midbrain dopaminergic innervation during development are unclear. Here, the authors showed that Nolz1 is required for axonal guidance of dopaminergic neurons during embryonic development of the mouse brain.
- Clement Soleilhavoup
- , Marco Travaglio
- & Lia Panman
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| Open AccessMutations in the KIF21B kinesin gene cause neurodevelopmental disorders through imbalanced canonical motor activity
Kinesins regulate intracellular transport and microtubule dynamics. Here, the authors show that KIF21B variants in humans associate with corpus callosum agenesis and microcephaly. Using mice and zebrafish, they showed the cellular mechanisms altered by the missense KIF21B variants.
- Laure Asselin
- , José Rivera Alvarez
- & Juliette D. Godin
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Article
| Open AccessLoss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy
UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.
- Holger Hengel
- , Célia Bosso-Lefèvre
- & Bruno Reversade
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| Open AccessFICD activity and AMPylation remodelling modulate human neurogenesis
Protein AMPylation is a post-translational modification whose implications in cellular physiology are not fully understood. Here the authors develop a cell-permeable AMPylation probe and use it to identify new AMP modified proteins and investigate the role of FICD in neuronal differentiation using cerebral organoids.
- Pavel Kielkowski
- , Isabel Y. Buchsbaum
- & Stephan A. Sieber
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| Open AccessDissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs
Here, authors present results of a hiPSC transcriptomics study on corticogenesis from multiple donors across four transitions in differentiation. They present a bulk data deconvolution method and show that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation.
- Emily E. Burke
- , Joshua G. Chenoweth
- & Andrew E. Jaffe
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| Open AccessAn early phase of instructive plasticity before the typical onset of sensory experience
Brain circuits exhibit different amounts of plasticity over different developmental stages. Here authors show that there is a transition of the influence of spatiotemporal patterns, from instructive to permissive, around the time of the onset of visual experience.
- Arani Roy
- , Shen Wang
- & Stephen D. Van Hooser
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| Open AccessDisruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.
- Hui Guo
- , Elisa Bettella
- & Evan E. Eichler
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Article
| Open AccessA cell fitness selection model for neuronal survival during development
Programmed cell death is an important part of tissue development, and traditionally it is considered that neuronal death is a stochastic process in response to neurotrophic factor deprivation. Here the authors show that for TrkC+ proprioreceptors, which neurons die is predetermined molecularly by how much TrkC is present, as well as by a gene expression signature.
- Yiqiao Wang
- , Haohao Wu
- & François Lallemend
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Article
| Open AccessImmature excitatory neurons develop during adolescence in the human amygdala
Immature excitatory neurons in the human amygdala persist throughout life and could be a substrate for plasticity. Here the authors find evidence that the maturation of these cells may be accelerated during puberty.
- Shawn F. Sorrells
- , Mercedes F. Paredes
- & Arturo Alvarez-Buylla
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Article
| Open AccessSphingolipid-dependent Dscam sorting regulates axon segregation
Little is known about the initial segregation of axonal and dendritic proteins during the differentiation of newly generated neurons. Here authors use a forward genetic screen to identify the role of sphingolipids in regulating the sub-cellular distribution of Dscam for neuronal patterning in Drosophila Mushroom Bodies
- Gaurav Goyal
- , Junfeng Zheng
- & Thomas Hummel
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| Open AccessSingle-cell transcriptomic analysis of mouse neocortical development
The authors perform single-cell RNA-seq of the mouse neocortex at an embryonic time point and at birth, and identify new and known cell types, and cell relatedness within and across age. These data serve as a resource to understand brain development and the cellular origins of brain diseases.
- Lipin Loo
- , Jeremy M. Simon
- & Mark J. Zylka
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Article
| Open AccessMFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size
It is unclear how and why axonal mitochondria are kept so small in axons. Authors show here that MFF-mediated fission is required for determining the size of mitochondria both entering and along the axon, and this is critical for mitochondrial calcium uptake capacity, neurotransmitter release properties and axon branching.
- Tommy L. Lewis Jr
- , Seok-Kyu Kwon
- & Franck Polleux
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Article
| Open AccessMouse MRI shows brain areas relatively larger in males emerge before those larger in females
Sex differences occur in various aspects of neurodevelopment. Here the authors use manganese-enhanced MRI at nine different postnatal stages to detail the development of structural sex differences in the mouse brain.
- Lily R. Qiu
- , Darren J. Fernandes
- & Jason P. Lerch
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Article
| Open AccessIdentification of genes associated with cortical malformation using a transposon-mediated somatic mutagenesis screen in mice
Cortical malformations have a variety of causes. Here the authors use transposon mutagenesis to insert mutations into neural stem cells in the developing mouse cortex to screen for new candidate genes for cortical malformation, and validate some targets in human brain tissue.
- I-Ling Lu
- , Chien Chen
- & Jin-Wu Tsai
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Article
| Open AccessPrecise temporal regulation of alternative splicing during neural development
The precise timing of neurodevelopmental splicing switches and the underlying regulatory mechanisms remain poorly understood. This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.
- Sebastien M. Weyn-Vanhentenryck
- , Huijuan Feng
- & Chaolin Zhang
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Article
| Open AccessDevelopmental increases in white matter network controllability support a growing diversity of brain dynamics
Human brain development is characterized by an increased control of neural activity, but how this happens is not well understood. Here, authors show that white matter connectivity in 882 youth, aged 8-22, becomes increasingly specialized locally and is optimized for network control.
- Evelyn Tang
- , Chad Giusti
- & Danielle S. Bassett
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| Open AccessPrecise inhibitory microcircuit assembly of developmentally related neocortical interneurons in clusters
Developmental neuroscientists have long asked if clonally-related neurons retain functional relationships after maturation. The authors show that sparsely labelled neocortical interneurons in clusters with high possibility of clonal relation preferentially form electrical, but not chemical, synapses.
- Xin-Jun Zhang
- , Zhizhong Li
- & Song-Hai Shi
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Article
| Open AccessDiscovery of long-range inhibitory signaling to ensure single axon formation
Emerging evidence suggests that gut microbiota influences immune function in the brain and may play a role in neurological diseases. Here, the authors offer in vivo evidence from a Drosophila model that supports a role for gut microbiota in modulating the progression of Alzheimer’s disease.
- Tetsuya Takano
- , Mengya Wu
- & Kozo Kaibuchi