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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 AccessExtracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity
Basal progenitors are enriched in gyrencephalic species like humans contributing to neuronal expansion. Here the authors show that LGALS3BP de novo variants are related to reduced cortical complexity and area in humans and that LGALS3BP regulates neural progenitor position in organoids, human fetal tissue and mice.
- Christina Kyrousi
- , Adam C. O’Neill
- & Silvia Cappello
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Article
| Open AccessIn situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain
Microglia remodel synapses and engulf apoptotic cells. The molecular program underlying these distinct functions are unclear. Here, the authors identify distinct microglial subsets associated with synaptic vs. neurogenic regions of the developing zebrafish brain.
- Nicholas J. Silva
- , Leah C. Dorman
- & Anna V. Molofsky
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Article
| Open AccessCHARGE syndrome protein CHD7 regulates epigenomic activation of enhancers in granule cell precursors and gyrification of the cerebellum
CHARGE syndrome that affects cerebellar development can be caused by haploinsufficiency of the chromatin remodeling enzyme CHD7; however the precise role of CHD7 remains unknown. Here the authors show CHD7 promotes chromatin accessibility and enhancer activity in granule cell precursors and regulates morphogenesis of the cerebellar cortex, where loss of CHD7 triggers cerebellar polymicrogyria.
- Naveen C. Reddy
- , Shahriyar P. Majidi
- & Harrison W. Gabel
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| 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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Article
| Open AccessProfilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.
- Elena E. Grintsevich
- , Giasuddin Ahmed
- & Jonathan R. Terman
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Article
| Open AccessFunctional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease
Non-human primate models of autism spectrum disorder (ASD) are few and not well characterised. Here, the authors describe synaptic function and gene expression changes in a marmoset model of ASD from birth to juvenile, highlighting its similarity to features observed in human ASD.
- Satoshi Watanabe
- , Tohru Kurotani
- & Noritaka Ichinohe
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Article
| Open AccessOligodendrocytic Na+-K+-Cl– co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain
Brain plasticity declines with age. Here, the authors show that NKCC1 regulates oligodendrocyte activity, facilitating neuronal plasticity during juvenile. Inducing activation of oligodendrocytic NKCC1 results in restoration of neuronal plasticity in the adult mouse brain.
- Yoshihiko Yamazaki
- , Yoshifumi Abe
- & Kenji F. Tanaka
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Article
| Open AccessTen-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain
Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.
- Ming Zhang
- , Jian Wang
- & Xianghui Zhao
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Article
| Open AccessExtensive transcriptional and chromatin changes underlie astrocyte maturation in vivo and in culture
Astrocytes have functions crucial for brain homeostasis, which are disrupted in many neurological disorders, but how these functions are established during astrocyte maturation is largely unknown. Here the authors show transcriptional and chromatin changes underlying astrocyte maturation in mice and identify transcription factors regulating maturation of cultured astrocytes.
- Michael Lattke
- , Robert Goldstone
- & Francois Guillemot
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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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Article
| Open Accessα-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.
- Xuan Xie
- , Shaogang Wang
- & Lan Bao
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Article
| Open AccessPreference uncertainty accounts for developmental effects on susceptibility to peer influence in adolescence
People often change their preferences to conform with others. Using a longitudinal design, the authors show that such conformity decreases over the course of adolescence and that this reduction in conformity is accompanied by a decreasing degree of uncertainty about what to like.
- Andrea M. F. Reiter
- , Michael Moutoussis
- & Raymond J. Dolan
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Article
| Open AccessCoordination of two enhancers drives expression of olfactory trace amine-associated receptors
In our nose, some neuron subpopulations express a family of trace amine associated receptors (TAARs, smelling e.g., rotten fish). Fei et al. identify two conserved enhancers across placental mammals named TAAR enhancer 1 and 2 that coordinately regulate expression of the entire Taar gene repertoire.
- Aimei Fei
- , Wanqing Wu
- & Qian Li
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Article
| 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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Article
| Open AccessInfant gut microbiome composition is associated with non-social fear behavior in a pilot study
Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.
- Alexander L. Carlson
- , Kai Xia
- & Rebecca C. Knickmeyer
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Article
| Open AccessCul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development
De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, the authors show that Cul3 is essential to regulate neuronal migration by tightly regulating Plastin3 (Pls3). Pls3 cell-autonomously regulates cell migration by regulating the actin cytoskeleton organization.
- Jasmin Morandell
- , Lena A. Schwarz
- & Gaia Novarino
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Article
| Open AccessCo-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids
The authors generate EMLOs (elongating multi-lineage organized gastruloids): organoids that self-organize to form compartments with characteristics of the central nervous system, peripheral nervous system, mesenchyme, and gut tube.
- Zachary T. Olmsted
- & Janet L. Paluh
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Article
| Open AccessFunctional and diffusion MRI reveal the neurophysiological basis of neonates’ noxious-stimulus evoked brain activity
The neurophysiological basis of neonatal responses to noxious stimulation is poorly understood. Using MRI, the authors observe that neonates’ noxious-stimulus evoked brain activity is coupled to both their resting-state network activity and white matter microstructure.
- Luke Baxter
- , Fiona Moultrie
- & Rebeccah Slater
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Article
| 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 AccessRHOA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex
Patients with Tuberous Sclerosis Complex (TSC) show aberrant wiring of neuronal connections. Here, the authors generate iPSC-derived neurons from patients with TSC. TSC2 +/− neurons show impaired mTOR-independent RhoA signaling-mediated axon guidance.
- Timothy S. Catlett
- , Massimo M. Onesto
- & Timothy M. Gómez
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Article
| Open AccessEfferent feedback controls bilateral auditory spontaneous activity
Spontaneous activity generated in the cochleae propagates into the central auditory system to promote circuit formation before hearing onset. Here, the authors reveal the important role of cholinergic efferent modulation in coordinating bilateral spontaneous activity and the emergence of functional responses.
- Yixiang Wang
- , Maya Sanghvi
- & Michael Crair
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Article
| Open AccessBrain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling
Lipophorin receptors (LpRs) regulate structural and functional development of neurons in Drosophila. Here authors demonstrate how short isoforms of LpR1 mediates astrocyte lipid shuttling to neuron through interacting with glia lipoprotein GLaz and the role of this pathway in dendritic morphogenesis in the fly brain.
- Jun Yin
- , Emma Spillman
- & Quan Yuan
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Article
| Open AccessIntracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain
During Drosophila development, two peaks of Notch activity propagate across the neuroepithelium to generate neuroblasts. Here, the authors show Notch cis-inhibition under the control of intracellular Notch trafficking establishes these two peaks, which temporally control neurogenesis in the brain.
- Miaoxing Wang
- , Xujun Han
- & Makoto Sato
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Article
| Open AccessLoss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration
Microglial SIRPα regulates synaptic pruning during development. Its role in neurodegeneration is unclear. Here, the authors show microglial SIRPα declines in the model of Alzheimer’s disease, leading to excessive microglia mediated synapse elimination as well as impaired cognitive function.
- Xin Ding
- , Jin Wang
- & Liang Li
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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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Article
| 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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Article
| Open AccessDistinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice
Molecular diversity of proprioceptive neuron types (Ia, Ib and II PNs) is unclear. Here, the authors characterized the functional organization and development of eight subtypes of PNs in mice. Importantly, Ia subtypes are plastic, suggesting a role in adaptive proprioception during motor behavior.
- Haohao Wu
- , Charles Petitpré
- & François Lallemend
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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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Article
| Open AccessChoroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development
Abnormal CSF accumulation in the brain can lead to hydrocephalus. The mechanisms regulating CSF clearance during early development are unclear. Here, the authors show that NKCC1 regulates the clearance of both CSF K+ and fluid volume through the choroid plexus during postnatal development in mice.
- Huixin Xu
- , Ryann M. Fame
- & Maria K. Lehtinen
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Article
| Open AccessA spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain
Alternative RNA splicing varies across the brain. Its mapping at single cell resolution is unclear. Here, the authors provide a spatial and single-cell splicing atlas reporting brain region- and cell type-specific expression of different isoforms in the postnatal mouse brain.
- Anoushka Joglekar
- , Andrey Prjibelski
- & Hagen U. Tilgner
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Article
| 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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Article
| Open AccessNeuronal processes and glial precursors form a scaffold for wiring the developing mouse cochlea
In developing embryos, axons grow through complex and dynamic terrains. Here, the authors show that spiral ganglion neurons in the developing mouse cochlea extend leading axons that interact with a scaffold of glial precursors, with follower axons fasciculating on top.
- N. R. Druckenbrod
- , E. B. Hale
- & L. V. Goodrich
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Article
| Open AccessDistinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury
The oligodendrocyte lineage is known for its transcriptional heterogeneity, but the functional consequences of this are unclear. Here, the authors show that distinct populations of mature oligodendrocytes have spatial preferences in the brain and spinal cord and show different responses to spinal cord injury.
- Elisa M. Floriddia
- , Tânia Lourenço
- & Gonçalo Castelo-Branco
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Article
| 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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Article
| Open AccessDevelopmental divergence of sensory stimulus representation in cortical interneurons
Sensory neuronal circuits adapt during maturation when animals start to actively interact with the external world. The authors reveal structural and functional rearrangements of the input cortical interneurons receive around the time the animals start active sensation.
- Rahel Kastli
- , Rasmus Vighagen
- & Theofanis Karayannis
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Article
| 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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Article
| Open AccessSynapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
Mossy fiber synapses are key in CA3 microcircuit function. Here, the authors profile the mossy fiber synapse proteome and cell-surface interactome. They uncover a diverse repertoire of cell-surface proteins and identify the receptor IgSF8 as a regulator of CA3 microcircuit connectivity and function.
- Nuno Apóstolo
- , Samuel N. Smukowski
- & Joris de Wit
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Article
| Open AccessMyelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits
Myelination optimizes conduction speed of excitatory neurons. However, whether myelination of interneurons (INs) refines cortical networks is unclear. Here, the authors show that INs myelination shapes feedforward inhibition of mouse cortical sensory circuits and impacts whisker-mediated behaviour.
- Najate Benamer
- , Marie Vidal
- & María Cecilia Angulo
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Article
| 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 AccessHippocampal hub neurons maintain distinct connectivity throughout their lifetime
In the neonatal hippocampus, GABA cells born the earliest operate as ‘hubs’ by orchestrating population synchrony. Here, the authors show that the earliest born GABAergic cells in the hippocampal CA1 region maintain distinct anatomical and functional properties throughout their lifetime.
- Marco Bocchio
- , Claire Gouny
- & Rosa Cossart
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Article
| Open AccessWrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila
Conduction velocity and precise neuronal transmission depend on axonal diameter and ephatic coupling, respectively. Here, the authors showed that wrapping glia regulates both conduction speed and precision of neuronal signalling in the Drosophila peripheral nervous system.
- Rita Kottmeier
- , Jonas Bittern
- & Christian Klämbt
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Article
| Open AccessThe cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development
The cellular and molecular mechanisms regulating hypothalamic patterning and differentiation are unclear. Here, the authors profiled the transcriptome of the developing hypothalamus at single cell level, providing a resource to hypothalamic development in health and disease.
- Dong Won Kim
- , Parris Whitney Washington
- & Seth Blackshaw
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Article
| Open AccessSingle cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates
The diversity of primary sensory neurons and how fate choice is determined is unclear. Here, the authors use single cell RNA sequencing analysis of early murine somatosensory neurons to show that sensory neuron diversity is achieved by a transition through a bi-potential intermediate state.
- Louis Faure
- , Yiqiao Wang
- & Saida Hadjab
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Article
| Open AccessCTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair
Myelination by Schwann cells (SC) in the peripheral nervous system is essential for motor function, and dysregulation of SC myelination can lead to various neuropathies. Here the authors describe a critical role of CCCTC-binding factor (CTCF)-dependent chromatin reorganization in peripheral myelination and myelin regeneration after injury.
- Jincheng Wang
- , Jiajia Wang
- & Q. Richard Lu
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Article
| Open AccessDscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain
Columns are the functional and morphological unit of the brain, but how neurons assemble into this structure was unclear. Here, the authors show that Dscam gene rewires neurons that derive from the same stem cell to establish columns through the process of lineage-dependent repulsion.
- Chuyan Liu
- , Olena Trush
- & Makoto Sato
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Article
| Open AccessCellular and molecular properties of neural progenitors in the developing mammalian hypothalamus
The hypothalamus performs a wide range of vital physiological functions, including growth and reproductive behaviors, and circadian rhythms. The authors identify and characterize hypothalamic radial glial and hypothalamic mantle zone radial glial cells as the neural progenitors in the hypothalamus.
- Xin Zhou
- , Suijuan Zhong
- & Xiaoqun Wang
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Article
| Open AccessAdolescent frontal top-down neurons receive heightened local drive to establish adult attentional behavior in mice
Frontal top-down cortical neurons implement top-down attentional control of sensory regions. The authors reveal adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are functionally integrated into local excitatory circuitry.
- Elisa M. Nabel
- , Yury Garkun
- & Hirofumi Morishita
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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