Featured
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Article
| Open AccessLinear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters
In neural progenitor cells, recurrent DNA break clusters (RDCs) occur to genes crucial for brain function. Here the authors find that most RDCs emerge at long-traveling unidirectional replication forks, and often unrelated to R-loops.
- Lorenzo Corazzi
- , Vivien S. Ionasz
- & Pei-Chi Wei
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Article
| Open AccessReconstruction of macroglia and adult neurogenesis evolution through cross-species single-cell transcriptomic analyses
Macroglia are neural cells that have garnered less interest than neurons despite their crucial functions including neurogenesis. Here the authors use sequencing from several species to investigate the evolution of macroglia and of adult neurogenesis.
- David Morizet
- , Isabelle Foucher
- & Laure Bally-Cuif
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Article
| Open AccessCondensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster
Mutations in condensin subunits cause microcephaly, but the underlying molecular mechanisms remain elusive. Here, the authors show that unrestricted retrotransposable element activity impairs brain development in condensin insufficient organisms.
- Bert I. Crawford
- , Mary Jo Talley
- & Michelle S. Longworth
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Article
| Open AccessThe SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation
Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here the authors characterize the interplay of these proteins and show that they coregulate neuronal target genes.
- Johannes Benedum
- , Vedran Franke
- & Dea Slade
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Article
| Open AccessTemporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity
PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.
- Anna Pagliaro
- , Roxy Finger
- & Benedetta Artegiani
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Article
| Open AccessAutophagy drives the conversion of developmental neural stem cells to the adult quiescent state
Neural stem cells in the adult mammalian brain derive from proliferating precursors that are spared as dormant reservoirs during development. Here, the authors show that autophagy is required for neural stem cells to transition to the adult quiescent state.
- Isabel Calatayud-Baselga
- , Lucía Casares-Crespo
- & Helena Mira
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Article
| Open AccessEmergence of task-related spatiotemporal population dynamics in transplanted neurons
Cell therapy is a promising treatment for brain injury, but it is unclear if transplanted neurons demonstrate population dynamics. By monitoring transplanted neurons in injured mice, here the authors show the emergence of dynamics resembling intact networks.
- Harman Ghuman
- , Kyungsoo Kim
- & Karunesh Ganguly
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Article
| Open AccessHMGA2 directly mediates chromatin condensation in association with neuronal fate regulation
High-mobility group AT-hook (HMGA) proteins 1 and 2 are nonhistone chromatin proteins involved in different biological processes. Here the authors reveal that HMGA2 is a bona fide chromatin condensation factor that undergoes liquid–liquid phase separation, and that its chromatin condensation activity is important for the maintenance of mouse neural progenitor cells.
- Naohiro Kuwayama
- , Tomoya Kujirai
- & Yukiko Gotoh
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Article
| Open AccessSubventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke
The functions of newborn cells arising from the subventricular zone in response to stroke have been unclear. Here, the authors show that cells migrating from the subventricular zone after stroke promote brain repair and functional recovery in mice.
- Michael R. Williamson
- , Stephanie P. Le
- & Michael R. Drew
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Article
| Open AccessTargeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development
Highly localized mechanical forces that shape in vivo tissue development remain challenging to recapitulate in vitro. Here the authors use magnetically actuated nanoparticles to generate spatially defined forces within organoids, which guide the spatial organization of tissue patterning and growth.
- Abdel Rahman Abdel Fattah
- , Niko Kolaitis
- & Adrian Ranga
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Article
| Open AccessCritical dynamics arise during structured information presentation within embodied in vitro neuronal networks
The conditions under which networks of neurons exhibit critical dynamics remains unclear. Here, the authors investigate how simple neural cultures reorganize activity when embodied in a gameplay environment and find that network wide neural criticality arises in nuanced ways.
- Forough Habibollahi
- , Brett J. Kagan
- & Chris French
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Article
| Open AccessSNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development
The balance of stem cell maintenance, differentiation, and programmed death is critical for proper development. Here they show that SNIP1 is critical for stem cell survival and differentiation in the developing brain where it acts downstream of TGFb and NFkB and regulates PRC2 activities for governing cell fates.
- Yurika Matsui
- , Mohamed Nadhir Djekidel
- & Jamy C. Peng
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Article
| Open AccessIntegrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology
The causes of ALS remain unclear with many proposed pathomechanisms. Here, the authors integrate iPSC-derived motor neuron and post-mortem datasets and identify a heightened DNA damage response accompanied by accumulation of somatic mutations in ALS.
- Oliver J. Ziff
- , Jacob Neeves
- & Rickie Patani
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Article
| Open AccessRedox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate
How reactive oxygen species regulate neuronal stem cell (NSC) behavior is poorly understood. Here, the authors report that Ncf1-dependent oxidation of Igfbp2 cystines represses DNA repair networks to regulate NSC self-renewal and cell fate decisions.
- Weam S. Shahin
- , Shima O. Ebed
- & John F. Engelhardt
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Article
| Open AccessNeural precursor cells tune striatal connectivity through the release of IGFBPL1
The physiological role of endogenous neural protenitor cells of the subventricular zone in adult stage is not fully understood. Here the authors show that in mice, these cells tune neuronal activity of the striatum via insulin-like growth factor binding protein-like 1 and cognitive functions.
- Erica Butti
- , Stefano Cattaneo
- & Gianvito Martino
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Article
| Open AccessCharacterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma
MYC amplification is an independent prognostic factor for the most aggressive subgroup (Group 3) of pediatric medulloblastoma (G3 MB). Here, the authors highlight the role of the RNA-binding protein, Musashi-1 (MSI1) in G3 MB and identify MSI1-bound targets sharing MYC associated pathways.
- Michelle M. Kameda-Smith
- , Helen Zhu
- & Sheila K. Singh
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Article
| Open AccessCBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder
Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects.
- Aurélie de Thonel
- , Johanna K. Ahlskog
- & Valérie Mezger
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Article
| Open AccessSingle cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
Single cell RNA-sequencing of the AstTau neuron-asteroid tau assembloid model reveals excitatory neuron inflammatory signatures and an astrocytic heat shock response similar to that occurring in the brains of individuals with tauopathies, which can be ameliorated with a neuroprotective HSP90 inhibitor.
- Hannah Drew Rickner
- , Lulu Jiang
- & Christine S. Cheng
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Article
| Open AccessModeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes
Our understanding of human brain development in health and disease is limited. The authors generated human brain organoids from stem cell-derived isolated single neural rosettes to study human cortico-striatal development and deficits caused by an autism-associated genetic abnormality in SHANK3.
- Yueqi Wang
- , Simone Chiola
- & Aleksandr Shcheglovitov
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Article
| Open AccessEffects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice
In this study, Pitonak et al. report that transplantation of neural progenitor cells derived from male donors trigger an immune rejection response following transplantation into sites of spinal cord injury in female mice.
- Michael Pitonak
- , Miriam Aceves
- & Jennifer N. Dulin
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Article
| Open AccessPrimary cilia and SHH signaling impairments in human and mouse models of Parkinson’s disease
Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.
- Sebastian Schmidt
- , Malte D. Luecken
- & Wolfgang Wurst
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Article
| Open AccessA brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours
The link between neural development and tumourigenesis in adult glioma remains unclear. Here, the authors monitor the developmental stages of Sox2 + /− stem cells from a mouse model using single-cell RNA sequencing and suggest the acquisition of embryonic-like states in the adult glioma development.
- Akram A. Hamed
- , Daniel J. Kunz
- & Peter B. Dirks
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Article
| Open AccessOrgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder
Cerebral organoids can be used to gain insights into neuropsychiatric disorders. Here the authors carry out RNAseq characterization from organoids derived from donors with autism spectrum disorder to identify associated cell type specific driver genes.
- Elaine T. Lim
- , Yingleong Chan
- & George M. Church
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Article
| Open AccessSignal requirement for cortical potential of transplantable human neuroepithelial stem cells
The regulatory pathways that control the human neural progenitor cell pool are not well understood. Here, Varga et al. identify signals that control the division of human pluripotent stem cell derived neural stem cells and their ability to make cortical neurons and glia.
- Balazs V. Varga
- , Maryam Faiz
- & Andras Nagy
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Article
| Open AccessMassively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation
How gene regulatory elements regulate gene expression during cellular differentiation remains largely unknown. Here the authors use perturbation-based massively parallel reporter assays at early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide different transcriptional patterns.
- Anat Kreimer
- , Tal Ashuach
- & Nadav Ahituv
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Article
| Open AccessElectrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
Paul George and colleagues developed a conductive polymer system to enable stem cell delivery and electrical modulation in vivo. Employing this system improved functional stroke recovery in rodents and identified important repair pathways.
- Byeongtaek Oh
- , Sruthi Santhanam
- & Paul M. George
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Article
| Open AccessA comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing
During development, neural progenitors generate a variety of neural types sequentially. Here the authors examine gene expression patterns in Drosophila neural progenitors at single-cell level, and identify a gene regulatory network controlling the sequential generation of different neural types.
- Hailun Zhu
- , Sihai Dave Zhao
- & Xin Li
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Article
| Open AccessSingle-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors
The decline in neurogenesis following birth is accompanied with a quiescent state characteristic of neural progenitors of the adult brain. Here, the authors identify the Wnt pathway antagonist SFRP1 as a potential signal that promotes quiescence and show that its inhibition stimulates stem cell activation.
- Vanessa Donega
- , Astrid T. van der Geest
- & Elly M. Hol
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Article
| Open AccessLipid droplet availability affects neural stem/progenitor cell metabolism and proliferation
Lipid droplets (LDs) are central to lipid metabolism, which is known to regulate neural stem cell behavior. Here, the authors show that LDs influence neural stem cell proliferation and metabolic activity and change upon differentiation or quiescence.
- Mergim Ramosaj
- , Sofia Madsen
- & Marlen Knobloch
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Article
| Open AccessCell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module
Adult neural stem cells are derived from an embryonic population of slowcycling progenitor cells, though how reduced cycling speed leads to establishment of the adult population has remained elusive. Here they show that non-oscillatory Notch-Hey signaling induced by slow-cycling contributes to long term maintenance of neural stem cells.
- Yujin Harada
- , Mayumi Yamada
- & Yukiko Gotoh
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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 AccessPHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
Here the authors identify PHF3 SPOC domain as a reader of the phosphorylated RNA polymerase II (Pol II) C-terminal domain. They show that PHF3 clusters with Pol II complexes in cells, drives phase separation of Pol II in vitro, and regulates neuronal gene expression and neuronal differentiation.
- Lisa-Marie Appel
- , Vedran Franke
- & Dea Slade
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Article
| Open AccessPlexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion
Biomechanical mechanisms orchestrating stem cell dynamics in development remain unclear. Here the authors show that guidance receptor Plexin-B2 organizes actomyosin contractility, cytoskeletal tension and adhesion during multicellular development of human embryonic stem cells and neuroprogenitor cells.
- Chrystian Junqueira Alves
- , Rafael Dariolli
- & Roland H. Friedel
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Article
| Open AccessLRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells
How neural stem cells can transition between states of proliferation and quiescence is unclear. Here, the authors identify Lrig1 as a specific marker for the primed quiescent state and demonstrate that Lrig1 maintains cells in a quiescent state via modulation of the EGFR pathway.
- María Ángeles Marqués-Torrejón
- , Charles A. C. Williams
- & Steven M. Pollard
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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 AccessLong-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition
Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. The authors show that in mice exposed to HMF, adult hippocampal neurogenesis and hippocampusdependent learning are impaired and could be rescued by restoring ROS levels.
- Bingfang Zhang
- , Lei Wang
- & Yongxin Pan
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Article
| Open AccessCellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification
Neural stem and progenitor cells (NSPCs) encounter constant stresses during aging, such as elevated oxidative stress. Here the authors show that oxidative stress induced reduction in NSPC neural differentiation is mediated by a FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signalling cascade initiated by FOXO3 oxidation.
- Inah Hwang
- , Hiroki Uchida
- & Jihye Paik
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Review Article
| Open AccessSteps towards standardized quantification of adult neurogenesis
Adult neurogenesis is involved in several physiological and pathological processes, however standardization for the quantification of new born neurons is lacking. Here, the authors provide guidance to improve reproducibility and rigour in cell quantification.
- Xinyu Zhao
- & Henriette van Praag
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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 AccessProlonged tau clearance and stress vulnerability rescue by pharmacological activation of autophagy in tauopathy neurons
Disruption of autophagy function in cellular and animal models of tauopathy increases tau aggregation. Here, the authors describe a small-molecule screen to identify compounds that promote autophagy clearance of tau and rescue disease-relevant phenotypes in tauopathy patient-derived neurons.
- M. Catarina Silva
- , Ghata A. Nandi
- & Stephen J. Haggarty
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Article
| Open AccessCYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment
Sequential generation of layer-specific cortical neurons requires radial glial cells (RGCs) to balance self-renewal and commitment. Here the authors show that RGCs and lineage committed progenitors are defined by distinct cell cycle phases and CYCLIN-B1/2 cooperates with CDK1 to activate Notch and maintain RGCs.
- Daniel W. Hagey
- , Danijal Topcic
- & Jonas Muhr
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Article
| Open AccessMethylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells
Gene regulation and metabolism co-ordinate self-renewal and differentiation of neural precursors (NPCs) in the developing brain. Here the authors show that methylglyoxal, a glycolytic intermediate metabolite, promotes GADPH-dependent translational repression of Notch1, thereby promoting NPC differentiation.
- Deivid Carvalho Rodrigues
- , Emily M. Harvey
- & Guang Yang
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Article
| 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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Article
| Open AccessJMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells
Neurogenesis is an ordered transition from pluriptotent cells to neural precursor cells (NPCs) to neurons. Here the authors show that loss of the lysine demethylases JMJD3 and UTX leads reduced DNA accessibility at neurogenesis loci in human NPCs, and that the chromatin remodeller BAF can rescue differentiation defects.
- Yongli Shan
- , Yanqi Zhang
- & Guangjin Pan
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Article
| Open AccessIncreasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
Ageing affects several brain areas causing a decrease in cognitive abilities and memory. We find that increasing the endogenous potential of the hippocampus to generate new neurons throughout life rejuvenates learning and memory, indicating that neural reserves can be exploited during ageing to compensate for age- or disease-related cognitive impairments.
- Gabriel Berdugo-Vega
- , Gonzalo Arias-Gil
- & Federico Calegari
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Article
| Open AccessEnhanced lysosomal degradation maintains the quiescent state of neural stem cells
It remains unclear why quiescent neural stem cells (qNSCs) in the subventricular zone of the mouse brain have enlarged lysosomes. Here, authors demonstrate that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs, which prevents the NSC exit from quiescence.
- Taeko Kobayashi
- , Wenhui Piao
- & Ryoichiro Kageyama
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Article
| Open AccessRestoration of visual function by transplantation of optogenetically engineered photoreceptors
A challenge in cell therapy for photoreceptor degeneration is inducing the grafted cells to grow and maintain light sensitive outer segments. Here, the authors use optogenetics to circumvent this problem and restore visual function in blind mice.
- Marcela Garita-Hernandez
- , Maruša Lampič
- & Jens Duebel
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Article
| Open AccessTBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex
The T-box protein TBR2 is involved in cortical neurogenesis expansion during neurodevelopment and is preferentially enriched in intermediate progenitors. The authors show that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly in the mouse cortex via PCDH19.
- Xiaohui Lv
- , Si-Qiang Ren
- & Song-Hai Shi
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Article
| Open AccessQuantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis
The single-cell gene expression changes during spinal cord formation and neurogenesis in mice are unclear. Here, the authors use a HES5 reporter to live image, then mathematically model, oscillations in single cells in presumed progenitors and neurons of the developing spinal cord.
- Cerys S. Manning
- , Veronica Biga
- & Nancy Papalopulu