Featured
-
-
Article
| Open AccessYoung adult-born neurons improve odor coding by mitral cells
Shani-Narkiss et al. established an experimental system to test the functional role of adult born neurons (ABNs) on Mitral Cell (MC) coding. Silencing ABNs, unexpectedly, quenched MC odor responses. A computational model provides a mechanistic explanation to the functional role of adult-born neurons in circuit computation of the olfactory bulb.
- H. Shani-Narkiss
- , A. Vinograd
- & A. Mizrahi
-
Article
| Open AccessSiah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy
In neural development, progenitors transition from a proliferative to a differentiated state. Here, the authors show that cerebellar granule neurons retract primary cilia as they exit their proliferative niche upon decreased ECM engagement, enabling radial migration due to loss of Shh sensitivity.
- Taren Ong
- , Niraj Trivedi
- & David J. Solecki
-
Article
| Open AccessDOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility
Neuronal differentiation requires rearrangement of the transcriptional and chromatin landscapes of neural cells. Here, the authors study in-vitro neuronal differentiation of murine embryonic stem cells (ESCs) to show that this process is modulated by DOT1L activity, which regulates H3K79me2 accumulation, and preserves accessibility of SOX2-bound enhancers.
- Francesco Ferrari
- , Laura Arrigoni
- & Thomas Manke
-
Article
| Open AccessABHD4-dependent developmental anoikis safeguards the embryonic brain
During embryonic development, neural progenitor cells undergo numerous cell divisions. Here, the authors show that ABHD4-mediated developmental anoikis distinguishes the physiological delamination and the pathological detachment of progenitor cells with relevance to fetal alcohol-induced apoptosis.
- Zsófia I. László
- , Zsolt Lele
- & István Katona
-
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
-
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
-
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
-
Article
| Open AccessYbx1 fine-tunes PRC2 activities to control embryonic brain development
Polycomb repressive complex 2 (PRC2) methylates H3K27 and suppresses RNA polymerase II transcription by promoting a closed chromatin. Here the authors identify the transcription factor Ybx1 as an interactor that regulates the binding of PRC2 to chromatin and H3K27 methylation to promote the genetic programs underlying neural lineages and neural progenitor self-renewal–differentiation choices.
- Myron K. Evans
- , Yurika Matsui
- & Jamy C. Peng
-
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
-
Article
| Open AccessDevelopmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Brain organoids are important tools to study early development and disease but little is known of their network activity and plasticity. Here the authors generate iPSC-derived neuronal organoids that display early network formation and maturation with evidence for a GABA polarity switch and long-term potentiation.
- Maria-Patapia Zafeiriou
- , Guobin Bao
- & Wolfram-Hubertus Zimmermann
-
Article
| Open AccessADNP promotes neural differentiation by modulating Wnt/β-catenin signaling
ADNP has been connected to neural developmental disorders. Here, the authors uncover a role for ADNP in neural induction and differentiation via β-Catenin stabilization, with ADNP disruption in zebrafish leading to defective neurogenesis and decreased Wnt signaling.
- Xiaoyun Sun
- , Xixia Peng
- & Yuhua Sun
-
Article
| Open AccessNeutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke
Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage. Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.
- Lijing Kang
- , Huilin Yu
- & Bing-Qiao Zhao
-
Article
| Open AccessPar complex cluster formation mediated by phase separation
The evolutionarily conserved complex, the Par proteins, regulates cell polarity. Here, the authors show that in Drosophila neuroblasts, the Par complex exhibits liquid–liquid phase separation dependent on the cell cycle.
- Ziheng Liu
- , Ying Yang
- & Wenyu Wen
-
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
-
Article
| Open AccessGlial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways
In the central nervous system, the maturation of glial cells is temporally and functionally coupled with that of the vascular network during postnatal development. Here the authors show that oligodendroglial HIFα regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling, while astroglial HIFα participates through Wnt-dependent signaling.
- Sheng Zhang
- , Bokyung Kim
- & Fuzheng Guo
-
Article
| Open AccessTransient microglial absence assists postmigratory cortical neurons in proper differentiation
Microglia temporarily disappear from the cortical plate in the midembryonic stage. This study demonstrated that microglial transient absence from the cortical plate is required for postmigratory neurons to appropriately fine-tune the expression of molecules needed for their proper differentiation.
- Yuki Hattori
- , Yu Naito
- & Takaki Miyata
-
Article
| Open AccessImprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development
How the imprinted Cdkn1c locus regulates corticogenesis is unclear. Here, the authors dissect the level of cell-autonomy of imprinted Cdkn1c gene function in mouse corticogenesis and identify this as regulating radial glial progenitor cell and projection neuron survival.
- Susanne Laukoter
- , Robert Beattie
- & Simon Hippenmeyer
-
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
-
Article
| Open AccessEarly dorsomedial tissue interactions regulate gyrification of distal neocortex
The contribution of long-range signaling to cortical gyrification remains poorly understood. In this study, authors demonstrate that the combined genetic loss of transcription factors Lmx1a and Lmx1b, expressed in the telencephalic dorsal midline neuroepithelium and head mesenchyme, respectively, induces gyrification in the mouse neocortex
- Victor V. Chizhikov
- , Igor Y. Iskusnykh
- & Kathleen J. Millen
-
Article
| Open AccessRBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury
Therapeutic hypothermia is a potent tool in the treatment of neonatal hypoxic-ischemic (HI) injury, yet the underlying mechanisms remain unclear. Here, authors demonstrate how the RNA-binding motif protein RBM3, which is induced by mild cooling while global translation rate is slowed down, contributes substantially to neuroregeneration after adult HI injury, specifically in the subventricular zone and subgranular zone.
- Xinzhou Zhu
- , Jingyi Yan
- & Sven Wellmann
-
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
-
Article
| Open AccessSensory cortex wiring requires preselection of short- and long-range projection neurons through an Egr-Foxg1-COUP-TFI network
Layer 4 spiny stellate cells project locally while pyramidal neurons have long-range projections yet the molecular program that determines their specificity is not yet known. Here, the authors demonstrate that Egr, Foxg1 and COUP-TFI transcription factors play causal role in the specification of these cell types.
- Pei-Shan Hou
- , Goichi Miyoshi
- & Carina Hanashima
-
Article
| Open AccessRegulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila
The patterning of sensory bristles on the dorsal thorax of flies is regulated by two transcription factor families but the dynamics of this regulation is unclear. Here, the authors visualize seven E(spl)-HLH proteins, showing their regulated expression promotes mutual inhibition by Notch during notum patterning.
- Lydie Couturier
- , Khalil Mazouni
- & François Schweisguth
-
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
-
Article
| Open AccessLzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development
Outer radial glial cells (oRGs) are undifferentiated cells that divide in the subventricular zone during neurodevelopment, but the underlying mechanisms are not fully understood. Here the authors show that Lzts1 positively controls both neuronal delamination and generation of oRG-like cell types.
- T. Kawaue
- , A. Shitamukai
- & A. Kawaguchi
-
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
-
Article
| Open AccessYin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner
The transcription factor Yin Yang 1 (YY1) plays an important role in human disease, yet little is known about its role in brain development. This study shows that YY1 controls cerebral cortex development by maintaining proliferation and survival of neural progenitor cells via transcriptional regulation of genes involved in metabolism and protein translation.
- Luis Zurkirchen
- , Sandra Varum
- & Lukas Sommer
-
Article
| Open AccessTUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis
New mutations and genes associated with malformations of cortical development keep being identified, yet there is little known about the underlying cellular mechanisms controlling these impairments. Here, authors generate and characterize a heterozygous TUBG1 knock-in mouse model bearing one of these known mutations and show that TUBG1 mutation leads to the miss-positioning of neurons in the cortical wall due to migration, because of defective microtubules dynamics, and not proliferation defects during corticogenesis.
- Ekaterina L. Ivanova
- , Johan G. Gilet
- & Maria-Victoria Hinckelmann
-
Article
| Open AccessTET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn
The potential role of TET proteins in adult neurogenesis is unknown. In this study, authors show that TET3 is essentially required for the maintenance of the NSC pool in the adult subventricular zone niche by preventing premature differentiation of NSCs, via direct binding and repression of the paternal transcribed allele of the imprinted gene Snrpn
- Raquel Montalbán-Loro
- , Anna Lozano-Ureña
- & Sacri R. Ferrón
-
Article
| Open AccessWNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
WNTs can signal over long distances but how this arises in the brain is unclear. Here, the authors show that WNT5A is secreted from the choroid plexus of the developing hindbrain (but not the telencephalon) and transported in the CSF with lipoprotein particles in order to control cerebellar morphogenesis.
- Karol Kaiser
- , Daniel Gyllborg
- & Vítězslav Bryja
-
Article
| Open AccessSingle-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development
Midbrain dopamine (mDA) neurons are significantly associated with Parkinson’s disease and yet there is no systematic molecular classification of these heterogenous group of cells. Here authors use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3 (broad mDA neuronal marker) to identify and characterize seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons.
- Katarína Tiklová
- , Åsa K. Björklund
- & Thomas Perlmann
-
Article
| Open AccessTranscriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma
In gene regulation, diversification at the transcriptome 3′end is linked to differentiation and dedifferentiation. Here, the authors discover extensive transcriptome 3′end-alterations in neuroblastoma, regulated by PCF11, and provide an interactive data repository of transcriptome-wide alternative polyadenylation.
- Anton Ogorodnikov
- , Michal Levin
- & Sven Danckwardt
-
Article
| Open AccessElevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects
Elevated maternal homocysteine (Hcy) increases the risk for neural tube defects (NTDs) but how this arises is unclear. Here, the authors show that high levels of Hcy on histone H3K79Hcy correlate with NTDs, causing abnormal gene expression (for example Cecr2, Smarca4 and Dnmt3B) linked to neural tube closure.
- Qin Zhang
- , Baoling Bai
- & Ting Zhang
-
Article
| Open AccessKIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development
The division of neural progenitors is closely regulated but how is unclear. Here, the authors show that mitotic kinesin KIF20A/MKLP2 interacts with a regulator of G protein signaling RGS3 in neural progenitor cells, dislodging it from the intercellular bridge of dividing cortical cells.
- Anqi Geng
- , Runxiang Qiu
- & Qiang Lu
-
Article
| Open AccessmTORC1 accelerates retinal development via the immunoproteasome
One of the determinants of the neuronal subtype produced from retinal progenitor cells is their proliferative potential. Here the authors show that mTORC1 promotes progenitor cell cycle progression and hence accelerated development in mouse retina through induction of the immunoproteasome which enhances the degradation of cyclins.
- Ji-Heon Choi
- , Hong Seok Jo
- & Jin Woo Kim
-
Article
| Open AccessReducing histone acetylation rescues cognitive deficits in a mouse model of Fragile X syndrome
Loss of fragile X mental retardation protein (FMRP) leads to fragile X syndrome, associated with cognitive dysfunction. Here the authors show that mice lacking FMRP show reduced hippocampal neurogenesis and cognitive deficits, which can be rescued by reducing histone acetylation.
- Yue Li
- , Michael E. Stockton
- & Xinyu Zhao
-
Article
| Open AccessSpatio-temporal relays control layer identity of direction-selective neuron subtypes in Drosophila
Direction-selective T4/T5 neurons show layer-specific projections in the fly visual circuit. Examining the mechanisms behind their development, the authors found that a relay of Wnt and Bmp signaling across neuroepithelial domains and transcription factor interactions specify T4/T5 subtype identity.
- Holger Apitz
- & Iris Salecker
-
Article
| Open AccessDlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons
In the hypothalamus, the arcuate nucleus (ARC) contains AgRP-neurons that regulate energy balance as well as GHRH-neurons that regulate linear growth. Here, the authors looked at how the transcription factors Dlx1/2 and Otp link development of AgRP- and GHRH-neurons.
- Bora Lee
- , Janghyun Kim
- & Jae W. Lee
-
Article
| Open AccessUncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus
Multiciliated ependymal cells (ECs) in the mammalian brain are glial cells facilitating cerebral spinal fluid movement. This study describes an inherent cellular plasticity of ECs as maintained by Foxj1 and IKK2 signaling, and shows resulting hydrocephalus when EC de-differentiation is triggered.
- Khadar Abdi
- , Chun-Hsiang Lai
- & Chay T. Kuo
-
Article
| Open AccessEnvironmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus
Environmental enrichment has functional and molecular effects on mammalian hippocampus. Here, Zhang and colleagues show that environmental enrichment of mice is correlated with dorsal-ventral asymmetry in transcription and DNA methylation of the dentate gyrus.
- Tie-Yuan Zhang
- , Christopher L. Keown
- & Michael J. Meaney
-
Article
| Open AccessImpairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses
Cholinergic neurons in the diagonal band of Broca degenerate early in Alzheimer’s disease. Here the authors show that in healthy mice, these cholinergic inputs innervate newborn neurons in the hippocampus, and that loss of this innervation in an Alzheimer’s disease model leads to impairments in spatial memory.
- Houze Zhu
- , Huanhuan Yan
- & Youming Lu
-
Article
| Open AccessTrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response
The precise mechanism for the sustained antidepressant action of ketamine is unclear. This study shows ketamine can promote neuronal differentiation via TrkB-ERK activation in mice and the sustained behavioral effect is attenuated when adult neurogenesis is blocked, but extended when it is enhanced.
- Zhenzhong Ma
- , Tong Zang
- & Luis F. Parada
-
Article
| Open AccessFBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development
Epithelial-to-mesenchymal transition (EMT) regulates both processes of organism development and changes in cell state causing disease. Here, the authors show that an E3 ubiquitin ligase, FBXO32, regulates EMT via CtBP1 and the transcriptional program, and also mediates cancer metastatic burden and neurogenesis.
- Sanjeeb Kumar Sahu
- , Neha Tiwari
- & Vijay K. Tiwari
-
Article
| Open AccessA post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
Unlike transcriptional regulation of hESC identity, little is known post-transcriptionally. Here, the authors show that the RNA binding protein CSDE1 regulates core components of hESC identity, neurectoderm commitment and neurogenesis to maintain pluripotency and prevent neural differentiation.
- Hyun Ju Lee
- , Deniz Bartsch
- & David Vilchez
-
Article
| Open AccessOxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons
Oxytocin (OXT) has been implicated in adult neurogenesis. Here the authors show that CA3 pyramidal cells in the adult mouse hippocampus express OXT receptors and receive inputs from hypothalamic OXT neurons; activation of OXT signaling in CA3 pyramidal cells promotes the survival and maturation of newborn neurons in the dentate gyrus in a non-cell autonomous manner.
- Yu-Ting Lin
- , Chien-Chung Chen
- & Kuei-Sen Hsu
-
Article
| Open AccessMicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord
In the spinal cord, someHox genes are transcribed in progenitors while their proteins are only detected in differentiating postmitotic motor neurons. Here, the authors show that miRNAs (specifically mir-27) regulate post-transcriptional Hoxa5 expression in motor neurons.
- Chung-Jung Li
- , Tian Hong
- & Jun-An Chen
-
Article
| Open AccessStage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors
The functions of semaphorins in the adult brain are poorly understood. Here the authors show that Sema7A carries out stage-specific functions in the adult hippocampus via differential receptor usage; in progenitor cells, Sema7A inhibits proliferation via acting on PlexinC1, whereas in adult-born neurons, it promotes dendrite growth through β1-integrins.
- Bart C. Jongbloets
- , Suzanne Lemstra
- & R. Jeroen Pasterkamp
-
Article
| Open AccessPervasive translational regulation of the cell signalling circuitry underlies mammalian development
Gene expression is regulated at several levels, including through the modulation of protein translation. Here the authors find that translation control diversifies gene expression between developing tissues and regulates major signalling pathways through a complex landscape of upstream open reading frames (uORFs).
- Kotaro Fujii
- , Zhen Shi
- & Maria Barna
-
Article
| Open AccessDynamic behaviour of human neuroepithelial cells in the developing forebrain
The dynamics of progenitor cells in human neocortex development has not been studied directly. Here, the authors timelapse image human neuroepithelial (NE) and radial glial (RG) cells in embryonic brain slices and find properties of NE cells and RG that are mimicked in cerebral organoids.
- Lakshmi Subramanian
- , Marina Bershteyn
- & Arnold R. Kriegstein