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A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia
The enteric nervous system encompasses the gut-intrinsic neuroglial networks that regulate gastrointestinal functions. Based on single-cell analysis, the authors propose a model in which neurogenic differentiation paths branch from a gliogenic trajectory.
- Anna Laddach
- , Song Hui Chng
- & Vassilis Pachnis
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| Open Access
An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis
Entosis is a process of cell cannibalism observed in cancer. Here, Sterling and colleagues report that entosis can also play a role in brain development and can contribute to the pathogenesis of microcephaly.
- Noelle A. Sterling
- , Jun Young Park
- & Seonhee Kim
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| Open Access
Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes
Astroblastoma (AB) is an uncommon brain tumour and its origin remains unknown. Here, the authors perform integrative molecular analysis of 35 AB-like tumours and provide evidence that these arise in the context of epigenetic and genetic changes in neural progenitors occurring during brain development.
- Norman L. Lehman
- , Nathalie Spassky
- & Akshitkumar M. Mistry
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| Open Access
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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| Open Access
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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| Open Access
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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| Open Access
The 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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| Open Access
Cellular 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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| Open Access
Methylglyoxal 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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| Open Access
Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion
The brain is a genomic mosaic shaped by somatic mutations and cellular responses that correct or purge these mutations. Here, by manipulating genome stability during embryonic brain development, authors revealed robust mechanisms that eliminate cells with genome damage from the brain, and the consequences of leaving somatic mutants unpurged
- Lei Shi
- , Adel Qalieh
- & Kenneth Y. Kwan
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| Open Access
Yin 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
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| Open Access
Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation
Sox2 regulates pluripotency in neural progenitor cells (NPC) but how protein stability affects this is unclear. Here, the authors identify changes in ubiquitylation of Sox2 (by CUL4A-DET1-COP1 ligase and OTUD7B deubiquitylase) as controlling protein stability and so the differentiation state of NPCs.
- Chun-Ping Cui
- , Yuan Zhang
- & Lingqiang Zhang
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| Open Access
Progressive divisions of multipotent neural progenitors generate late-born chandelier cells in the neocortex
Diverse GABAergic neurons arise from progenitors in the medial ganglionic eminence. Here, the authors show these progenitors are progressively fate-restricted, with early-born interneurons occupying cortex in an “inside-out” pattern and later-born types like chandelier cells generated “outside-in”.
- Khadeejah T. Sultan
- , Wenying Angela Liu
- & Song-Hai Shi
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| Open Access
Dynamic 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
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| Open Access
Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages
Human mutations in the NDE1 gene have been associated with cortical malformations and severe microcephaly. Here, the authors show in embryonic rat brains that NDE1-depleted neural progenitors arrest at three specific cell cycle stages before mitosis, resulting in a severe decrease in neurogenesis.
- David J. Doobin
- , Shahrnaz Kemal
- & Richard B. Vallee
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| Open Access
Identification of proliferative progenitors associated with prominent postnatal growth of the pons
Postnatal growth of the pons is not well characterized. Here the authors show that growth of the murine pons is fastest during postnatal day 0–4, a period preceding myelination, and is primarily driven by an expansion of the oligodendrocyte population that derive from Sox2+Olig2+progenitors.
- Robert A. Lindquist
- , Cristina D. Guinto
- & Arturo Alvarez-Buylla
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| Open Access
Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells
The molecular mechanisms determining the temporal identity patterns of self-renewing progenitors during cerebral development are largely unclear. Here, using single cell transcriptome analyses, the authors find progenitor temporal identity arises independent of cell-cycle progression and Notch activation.
- Mayumi Okamoto
- , Takaki Miyata
- & Ayano Kawaguchi
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| Open Access
Feedback regulation of apical progenitor fate by immature neurons through Wnt7–Celsr3–Fzd3 signalling
The switch from neurogenesis to gliogenesis in cortical development is only partially understood. Here the authors show that Wnt-Planar cell polarity signaling in immature cortical neurons activates Notch in neural progenitor cells, thereby tuning the timing of their fate decisions.
- Wei Wang
- , Yves Jossin
- & Andre M. Goffinet
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| Open Access
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin
The extracellular matrix is suggested to play a role in neurogenesis, but it is unclear what role integrin signalling may play in the developing neuroepithelium. Here, in chick, Long et al. show that expression of constitutively active integrin beta-1 enhances neurogenesis via a novel Wnt7 and decorin pathway.
- K. Long
- , L. Moss
- & C. ffrench-Constant
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| Open Access
Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2
Neuron differentiation is marked by changes in intracellular redox status. Here Yan et al. show that ER-resident peroxiredoxin 4 senses increased H2O2and prevents the surface expression of differentiation-promoting GDE2 by modifying cysteine residues within GDE2.
- Ye Yan
- , Cynthia Wladyka
- & Shanthini Sockanathan
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Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells
Applications of human pluripotent stem cells (hPSCs) for disease modelling or cell therapy are hindered by low efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs). Here the authors develop a method to derive highly pure motor neuron progenitor populations from human embryonic and induced pluripotent stem cells that yield functional MNs.
- Zhong-Wei Du
- , Hong Chen
- & Su-Chun Zhang
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| Open Access
Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors
Profiling pluripotent stem cell (PSC)-derived neural progeny is of fundamental interest for characterizing stem cell differentiation. Here, the authors analyse neural progenitors consecutively derived from human PSCs, showing dynamic stage-specific transcriptional patterns for distinct neural progenitors.
- Reuven Edri
- , Yakey Yaffe
- & Yechiel Elkabetz
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Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex
Microglia colonize germinal regions of the developing cerebral cortex and contribute to the regulation of neurogenesis but the mechanisms that regulate this are not clear. Here the authors show that brain progenitor cells, through the secretion of the chemokine Cxcl12, drive microglia to cluster into the germinal regions of the developing mouse cerebral cortex.
- Benedetta Arnò
- , Francesca Grassivaro
- & Luca Muzio
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Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum
GABAergic neuron progenitors in the cerebellum give rise to Purkinje cells and GABAergic interneurons. Here the authors show that the transcription factors Olig2 and Gsx1 regulate an identity transition from Purkinje cell progenitors to interneuron progenitors during mouse development.
- Yusuke Seto
- , Tomoya Nakatani
- & Mikio Hoshino
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The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors
The E3-ubiquitin ligase APC/C and its cofactor Cdh1 have been shown to play important roles in axonal growth and synaptic plasticity. In this study, Eguren et al.show that elimination of Cdh1 in the developing nervous system results in defects in the neural progenitor compartment, hydrocephalus and reduced lifespan.
- Manuel Eguren
- , Eva Porlan
- & Marcos Malumbres
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APC/C-Cdh1 coordinates neurogenesis and cortical size during development
The E3 ubiquitin ligase APC/C plays a critical role in cell cycle progression. In this study, Delgado-Esteban et al. show that APC/C bound to the co-factor Cdh1 is necessary for neural progenitor cell maintenance and neuronal differentiation.
- Maria Delgado-Esteban
- , Irene García-Higuera
- & Angeles Almeida
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| Open Access
α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors
De novoneurogenesis occurs within the adult hypothalamus, suggesting the existence of a local neural stem cell niche. Here, the authors show that α-tanycytes lining the third ventricle are self-renewing multipotent neural stem cells, whose proliferation is dependent upon local FGF signalling.
- S.C. Robins
- , I. Stewart
- & M. Placzek
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| Open Access
Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc
Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.
- Daisuke Sakai
- , Yoshihiko Nakamura
- & Joji Mochida
Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster