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Developmental basis of SHH medulloblastoma heterogeneity
The role of developmental pathways in medulloblastoma tumours (MB) with sonic hedgehog (SHH) activation remains to be explored. Here, the authors perform multi-omic analysis and characterise the key transcriptomic and metabolic patterns of highly differentiated cells in SHH MBs.
- Maxwell P. Gold
- , Winnie Ong
- & Ernest Fraenkel
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Article
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Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina
The molecular mechanisms controlling injury-dependent neuronal regeneration are largely unknown. Here, the authors use integrated multiomic analysis to characterize gene regulatory networks controlling injury-induced neurogenesis in zebrafish retina
- Pin Lyu
- , Maria Iribarne
- & Seth Blackshaw
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Mechanical control of neural plate folding by apical domain alteration
Theoretical and experimental observations argue that apical domain heterogeneity in the neural plate is a tug-of-war contest between constricted and elongated cells. This competition likely reflects mechanical forces operating during tissue bending.
- Miho Matsuda
- , Jan Rozman
- & Sergei Y. Sokol
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KDM2B 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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Subventricular 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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Non-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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Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice
Exercise has positive effects on the brain during aging. Here the authors show that in mice, platelet-released exerkine PF4 mediates the effects of exercise on the brain.
- Odette Leiter
- , David Brici
- & Tara L. Walker
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NvPrdm14d-expressing neural progenitor cells contribute to non-ectodermal neurogenesis in Nematostella vectensis
Endodermal neurogenesis is an uncommon trait among animals. Here they identify a population of endoderm-specific neural progenitor cells in the cnidarian Nematostella vectensis that is characterized by the expression of the transcription factor prdm14d.
- Quentin I. B. Lemaître
- , Natascha Bartsch
- & Fabian Rentzsch
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SNIP1 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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Spatiotemporal proteomic atlas of multiple brain regions across early fetal to neonatal stages in cynomolgus monkey
Proteomic data covering fetal and neonatal primate brain development in the primate brain is needed to understand development and changes in functional gene products. Here, the authors show the dynamic proteomic changes of the cynomolgus macaque brain during the development from early fetal to neonatal stages by constructing a spatiotemporal proteomic atlas.
- Jingkuan Wei
- , Shaoxing Dai
- & Wei Si
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Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition
The usage of specific distal regulatory regions within the genome is critical for fate specification and cell maturation. Here, the authors show that the accumulation of the oncoprotein SET, as occurring in the rare Schinzel-Giedion syndrome, and associated histone hypo-acetylation interfere with normal enhancer repertoire employed during brain development.
- Mattia Zaghi
- , Federica Banfi
- & Alessandro Sessa
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Asymmetric activity of NetrinB controls laterality of the Drosophila brain
Brain asymmetry is widespread across species, but its function remains poorly understood. Here, the authors show that the Netrin axon guidance pathway is involved in building an asymmetric neural circuit important for long-term memory in Drosophila.
- F. Lapraz
- , C. Boutres
- & S. Noselli
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Redox-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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Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis
Here the authors identify RNA-binding protein MEX3A as a post-transcriptional regulator of quiescence and differentiation signatures at critical transitions along the murine subependymal neurogenic lineage
- Ana Domingo-Muelas
- , Pere Duart-Abadia
- & Isabel Fariñas
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CBP-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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Immature olfactory sensory neurons provide behaviourally relevant sensory input to the olfactory bulb
New olfactory sensory neurons (OSNs) wire into highly organized olfactory bulb circuits throughout life. Here, the authors show that immature OSNs provide behaviourally relevant sensory input to olfactory bulb neurons that is functionally distinct from that provided by mature OSNs.
- Jane S. Huang
- , Tenzin Kunkhyen
- & Claire E. J. Cheetham
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MTG8 interacts with LHX6 to specify cortical interneuron subtype identity
There is a large diversity of inhibitory interneurons in the mammalian cerebral cortex. How this emerges during embryogenesis remains unclear. Here, the authors identify MTG8 as a co-factor of LHX6 and a new regulator of cortical interneuron development.
- Zeinab Asgarian
- , Marcio Guiomar Oliveira
- & Nicoletta Kessaris
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Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks
Traumatic brain injury can cause long-term disability and thus constitutes a substantial healthcare burden worldwide. Here, the authors report a conductive microporous hydrogel to improve angiogenesis and recovery of brain function in traumatic brain lesions.
- Ru-Siou Hsu
- , Ssu-Ju Li
- & Shang-Hsiu Hu
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Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis
The mechanisms that govern cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Here the authors present a spatiotemporal single-cell regulatory atlas tracking these cells’ dental lineage diversification.
- Junjun Jing
- , Jifan Feng
- & Yang Chai
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Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex
HNRNPU is an RNA splicing protein associated with brain disorders such as early onset seizures. Here they show that HNRNPU functions to maintain neural progenitors and their progeny by regulating splicing of key neuronal genes.
- Tamar Sapir
- , Aditya Kshirsagar
- & Orly Reiner
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An 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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Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery
Stem cell based replacement therapies could provide a treatment for Parkinson’s disease. Here the authors outline a retinoic acid-based approach for robust derivation of dopamine neurons from stem cells that restore motor deficits in parkinsonian rats.
- Zhanna Alekseenko
- , José M. Dias
- & Johan Ericson
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Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development
The Dlgap protein family members are known for their role in synapses. Here the authors reveal important involvement in earlier steps of brain development, identifying DLGAP4 mutations in patients with cortical malformations, and also demonstrating a role in progenitors and migrating neurons.
- Delfina M. Romero
- , Karine Poirier
- & Fiona Francis
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Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans
Mitochondrial deficiency causes rare incurable disorders. Here, the authors use C. elegans to study these diseases and find that the natural compound lutein prevents neurodevelopmental deficits, thus pointing to a possible therapeutic target for the human diseases.
- Silvia Maglioni
- , Alfonso Schiavi
- & Natascia Ventura
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Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
Rawat et al. demonstrate that activation of adult-born immature hippocampal neurons is necessary and sufficient for the acute antidepressant effects of low-dose ketamine in mice.
- Radhika Rawat
- , Elif Tunc-Ozcan
- & John A. Kessler
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Reduced chromatin accessibility correlates with resistance to Notch activation
Notch signalling plays a key role in cell fate transitions, but how Notch activates distinct regulatory networks in closely related cell types is not well understood. Here the authors profile Notch and RBPJ targets in the developing mouse cortex and reveal how transcription factor occupancy and chromatin remodelling interact to direct differential gene expression during differentiation.
- Jelle van den Ameele
- , Robert Krautz
- & Andrea H. Brand
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A 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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Precision of morphogen gradients in neural tube development
Morphogen gradients encode positional information during development. Here the authors use theory and simulations to suggest a positional accuracy of single gradients that directly explains the observed precision of progenitor domain boundaries.
- Roman Vetter
- & Dagmar Iber
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Single-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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The 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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Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells
The temporal development of tissues and organs may be defined by the genome-wide epigenetic and transcriptional state functioning as the clock. Here the authors found that Fbl, a ribosomal RNA methyltransferase, potentially behaves as a clock during neural stem cell (NSC) development by controlling translational efficiencies of epigenetic modifiers in the cerebral cortex primordium.
- Quan Wu
- , Yuichi Shichino
- & Fumio Matsuzaki
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Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis
The evolutionary point where chromatin modifier function integrated into regulation of specific cell types is unclear. In the cnidarian Nematostella vectensis, the authors here show that lysine specific demethylase Lsd1 is developmentally regulated and required for normal development including cnidocyte differentiation.
- James M. Gahan
- , Ian U. Kouzel
- & Fabian Rentzsch
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Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants
Coordinated programs of gene expression drive brain development. Here, the authors use human embryonic stem cells and foetal cortical tissue as well as available GWAS statistics and analysis of genetic variants associated with neuropsychiatric disorders and cognition revealing a convergence on transcriptional programs regulating excitatory cortical neurogenesis.
- Bret Sanders
- , Daniel D’Andrea
- & Eunju Shin
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Identification of a modular super-enhancer in murine retinal development
Super-enhancers are regions of genomic DNA comprised of multiple putative enhancers that contribute to dynamic gene expression patterns during development. Here the authors identify a modular super-enhancer in murine retinal development and show that distinct modules are responsible for retinal progenitor cell proliferation during early and bipolar neuron genesis during late retinal development.
- Victoria Honnell
- , Jackie L. Norrie
- & Michael A. Dyer
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Temperature sensitivity of Notch signaling underlies species-specific developmental plasticity and robustness in amniote brains
Ambient temperature significantly affects embryogenesis, but adaptive molecular mechanisms that respond to temperature remain unclear. Here, the authors identified species-specific thermal sensitivity of Notch signaling in developing amniote brains.
- Tadashi Nomura
- , Kohjiro Nagao
- & Katsuhiko Ono
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Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly
Mutations in the human WDR81 gene result in severe microcephaly. Carpentieri et al. show that mutation of WDR81, a gene coding for an endosomal regulator, alters intracellular processing of the EGF receptor, leading to reduced proliferation rates of neuronal progenitors and to microcephaly.
- Jacopo A. Carpentieri
- , Amandine Di Cicco
- & Alexandre D. Baffet
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Lipid 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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Cell 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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Locomotion dependent neuron-glia interactions control neurogenesis and regeneration in the adult zebrafish spinal cord
The mechanisms stimulating adult neurogenesis are unclear. Here, the authors show the contribution of cholinergic and GABAergic signalling within the locomotor network to spinal cord neurogenesis during homeostasis and regeneration, showing neurogenesis depends on circuit activity in the adult zebrafish.
- Weipang Chang
- , Andrea Pedroni
- & Konstantinos Ampatzis
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Article
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Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids
Brain organoids derived from human pluripotent stem cells can model human brain development and disease, though current culture systems fail to ensure reliable production of high-quality organoids. Here the authors combine human brain extracellular matrix and culture in a microfluidic device to promote structural and functional maturation of human brain organoids.
- Ann-Na Cho
- , Yoonhee Jin
- & Seung-Woo Cho
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Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype
Subunits of the Elongator complex have been implicated in several nervous system pathologies. Here, the authors identify ELP2 variants in six patients with neurodevelopmental anomalies and show in mouse models that these variants impact protein stability and the activity of the complex during brain development.
- Marija Kojic
- , Tomasz Gawda
- & Brandon J. Wainwright
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Article
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Intracellular 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
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Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats
The role of adult hippocampal neurogenesis in memory reconsolidation is unclear. Here, the authors show that memory retrieval activates both immature and mature adult-born neurons. However, only adult-born neurons immature during learning are required for remote memory reconsolidation in rats.
- Marie Lods
- , Emilie Pacary
- & Sophie Tronel
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Article
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A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy
Adult-born granule cells integrate in hippocampal circuitry and contribute to hippocampal function. Here, the authors show that a critical period of neuronal activity regulates aberrant neurogenesis to rewire hippocampal circuitry and drive seizures in a mouse model of epilepsy.
- Zane R. Lybrand
- , Sonal Goswami
- & Jenny Hsieh
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Single-cell transcriptomic reveals molecular diversity and developmental heterogeneity of human stem cell-derived oligodendrocyte lineage cells
Brain myelinating oligodendrocytes are rare and difficult to isolate, which has limited data on their development. Here the authors develop a reporter for scalable purification of human pluripotent stem cell derived oligodendrocyte lineage cells, and use this to map differentiation using single cell RNA-sequencing,
- Xitiz Chamling
- , Alyssa Kallman
- & Donald J. Zack
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Article
| Open Access
The 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
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Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system
The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.
- Grégoire Chevalier
- , Eleni Siopi
- & Pierre-Marie Lledo
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Article
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Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy
The dentate gyrus is involved in synchronous discharges and seizures, but its microcircuit functional organization in TLE is unclear. Here, the authors show that interictal discharges recruit specific granule cell ensembles dominated by adult-born immature neurons.
- F. T. Sparks
- , Z. Liao
- & A. Losonczy
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Article
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STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells
STRAP (serine threonine kinase receptor-associated protein) promotes tumorigenicity. Here the authors report that STRAP associates with spliceosome and regulates alternative splicing during embryonic stem cell lineage commitment and early mouse embryo organogenesis.
- Lin Jin
- , Yunjia Chen
- & Pran K. Datta
Noncanonical function of folate through folate receptor 1 during neural tube formation