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| Open AccessSpatiotemporal 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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Article
| Open AccessSubcellular second messenger networks drive distinct repellent-induced axon behaviors
Signals from extracellular cues orienting growing axons are thought to be integrated by second messenger molecules. Here, Baudet et al. instead demonstrate that distinct axon guidance cues induce cAMP, cGMP and Ca2+ signals restricted to separate cellular nanodomains.
- Sarah Baudet
- , Yvrick Zagar
- & Xavier Nicol
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Article
| Open AccessElevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway
MAP1B is bound and regulated by fragile X protein FMRP. Here, the authors show that elevated levels of MAP1B reduce the morphological and physiological maturation of human neurons and impair social behavior in mice.
- Yu Guo
- , Minjie Shen
- & Xinyu Zhao
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Article
| Open AccessSchizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids
Copy number deletions in 2p16.3 locus (NRXN1) in individuals significantly increase risk for schizophrenia. Here, authors show, at single cell level, genetic background-specific effects that culminate in synaptic dysfunction using iPSC-derived brain organoid model.
- Rebecca Sebastian
- , Kang Jin
- & ChangHui Pak
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Article
| Open AccessFour-dimensional mapping of dynamic longitudinal brain subcortical development and early learning functions in infants
Studies of early brain development often rely on cross sectional data. Here the authors investigate volumetric development and surface area expansion of six subcortical structures using longitudinal MRI scans within the first two postnatal years.
- Liangjun Chen
- , Ya Wang
- & Gang Li
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Article
| Open AccessPIE-seq: identifying RNA-binding protein targets by dual RNA-deaminase editing and sequencing
Tracking protein-RNA interaction across cell types is challenging. Here, Ruan et al develop a dual-deaminase method called PIE-Seq, where protein targets are marked by both C-to-U and A-to-I RNA base editors, and apply it to 25 human RNA-binding proteins.
- Xiangbin Ruan
- , Kaining Hu
- & Xiaochang Zhang
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Article
| Open AccessCircadian regulation of developmental synaptogenesis via the hypocretinergic system
Whether the circadian clock regulates early developmental processes is poorly understood. Here, the authors report the circadian rhythm of synapse formation during early brain development by using the retinotectal system of larval zebrafish as an in vivo model.
- Xu-Fei Du
- , Fu-Ning Li
- & Jiu-Lin Du
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Article
| Open AccessNeonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment
Early life inflammation has been linked to neurodevelopmental outcomes. Here the authors show that in mice, neonatal immune challenge results in CD3 + T cell infiltration to brain parenchyma, and microglial activation, to a greater extent in males than females.
- Marius Schwabenland
- , Omar Mossad
- & Thomas Blank
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Article
| Open AccessAnatomical and functional maturation of the mid-gestation human enteric nervous system
Dershowitz and colleagues assess second trimester human fetal enteric nervous system development and function. They describe structural reorganization of the enteric nervous system that corresponds to gastrointestinal motility onset in ex vivo preparations.
- Lori B. Dershowitz
- , Li Li
- & Julia A. Kaltschmidt
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Article
| Open AccessComplex computation from developmental priors
Neuroscience has long inspired AI, however the neuroevolutionary search that produces sophisticated behaviors has not been systematized. This paper defines neurodevelopmental ML as a discovery process for structures that promote complex computations.
- Dániel L. Barabási
- , Taliesin Beynon
- & Nicolas Perez-Nieves
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Article
| Open AccessAsymmetric 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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Article
| Open AccessJNK signaling in pioneer neurons organizes ventral nerve cord architecture in Drosophila embryos
The shape and size of the mature central nervous system is highly regular, implying precise architectural rules. The authors show that alterations in JNK signaling in selected neurons impact the overall 3-dimensional organization of the Drosophila ventral nerve cord in a cell non-autonomous fashion.
- Katerina Karkali
- , Timothy E. Saunders
- & Enrique Martín-Blanco
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Article
| Open AccessGold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain
Cerebrospinal fluid (CSF) is essential for brain development. Here, the authors use gold nanoparticle enhanced X-ray microtomography to map CSF distribution in post-natal rodents and describe particle size-dependent CSF pathways that transport CSF into the brain parenchyma of rodents.
- Shelei Pan
- , Peter H. Yang
- & Jennifer M. Strahle
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Article
| Open AccessAn 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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Article
| Open AccessSingle-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons
How molecular diversity in neurons links to versatile functions is elusive. Here the authors profiled embryonic spinal motor neurons with single-cell RNAseq and identified molecular subtypes targeting distinct muscle groups in different species.
- Ee Shan Liau
- , Suoqin Jin
- & Jun-An Chen
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Article
| Open AccessSt18 specifies globus pallidus projection neuron identity in MGE lineage
The medial ganglionic eminence produces both interneurons and projection neurons, though how this fate choice is made is not well established. Here they show that St18 regulates migration and morphology of MGE neurons, inducing projection neuron fates.
- Luke F. Nunnelly
- , Melissa Campbell
- & Edmund Au
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Article
| Open AccessAn atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics
Late prenatal development of the human neocortex encompasses a critical period of gliogenesis and cortical expansion. Here, authors use human transcriptomics to capture transience and diversity of cells in middle and late prenatal development, including glial progenitor signatures.
- Susana I. Ramos
- , Zarmeen M. Mussa
- & Nadejda M. Tsankova
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Article
| Open AccessCell type diversity in a developing octopus brain
The brain cell types of Octopus vulgaris that control their sophisticated behavioral repertoire are still unknown. Here, authors use single-cell transcriptomics to profile neuronal and glial cell types and compare cell type relationships within the octopus brain and across species.
- Ruth Styfhals
- , Grygoriy Zolotarov
- & Eve Seuntjens
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Article
| Open AccessIdentification of visual cortex cell types and species differences using single-cell RNA sequencing
The laminar organization of macaque V1 cortex is similar to that seen in humans. Here the authors describe a single-cell RNA sequencing dataset of macaque V1 cortex cells.
- Jia-Ru Wei
- , Zhao-Zhe Hao
- & Sheng Liu
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Article
| Open AccessDevelopmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model
Brain-wide mapping of synapse molecular composition in Pax6 mutant mice shows remodelling and restoration of synaptome architecture during development, a possible means of conferring resilience to genetic disorders.
- Laura Tomas-Roca
- , Zhen Qiu
- & Seth G. N. Grant
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Article
| Open AccessMolecular identity of proprioceptor subtypes innervating different muscle groups in mice
The molecular basis of proprioceptive neuron subtype identities is not fully understood. Here the authors investigate diversity of proprioceptive neurons connected to different muscles at the molecular level, and show that acquisition of muscle-type identity precedes the emergence of receptor character and contains effectors controlling muscle connectivity.
- Stephan Dietrich
- , Carlos Company
- & Niccolò Zampieri
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Article
| Open AccessErratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex
During development, astrocytes are generated from radial glia, and migrate to the cortical plate, but the process of astrocyte migration during development is not fully understood. Here the authors labelled cells derived from the cortical ventricular zone in the late stages of cortical plate development in mice, and identified a migration mode in which cells move rapidly and almost at random within the intermediate zone and the cortical plate.
- Hidenori Tabata
- , Megumi Sasaki
- & Kazunori Nakajima
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Article
| Open AccessFunction of bidirectional sensitivity in the otolith organs established by transcription factor Emx2
The inner ear is highly organized, with distinct domains being located across the Line of Polarity Reversal (LPR). Here they show that Emx2 establishes the LPR and bidirectional selectivity of otolith organs, and that loss of the LPR in mice affects swimming and balance.
- Young Rae Ji
- , Yosuke Tona
- & Doris K. Wu
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Article
| Open AccessMaintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism
To remain functional throughout life, neuronal cells must maintain the ability to synthesize and release specific neurotransmitters. Here, the authors show that this ability critically depends on the activity of Hox proteins.
- Weidong Feng
- , Honorine Destain
- & Paschalis Kratsios
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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 AccessTranscriptional dynamics of murine motor neuron maturation in vivo and in vitro
Patel et al. show that gene expression and regulation in motor neurons is dynamic until juvenile age. A core subprogram (~40% of genes) is faithfully recapitulated in cultured motor neurons, with neuronal activity playing only a modulatory role.
- Tulsi Patel
- , Jennifer Hammelman
- & Hynek Wichterle
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Article
| Open AccessMTG8 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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Article
| Open AccessA Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes
Children with type 1 diabetes (T1D) are at risk for reduced cognitive ability and atypical brain development. This study shows that brain and cognitive measures can be improved in adolescents with T1D using a semi-automated insulin delivery system.
- Allan L. Reiss
- , Booil Jo
- & Juan Marrero
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Article
| Open AccessSirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia
Neonatal hypoxia leads to white matter hypomyelination due to delayed oligodendrocyte maturation. The authors identify Sirt2 as a crucial regulator of oligodendrocyte differentiation during normal white matter development and in response to hypoxia.
- Beata Jablonska
- , Katrina L. Adams
- & Vittorio Gallo
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Article
| Open AccessPregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice
During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.
- Steven Schepanski
- , Mattia Chini
- & Petra C. Arck
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Article
| Open AccessHeterogeneous 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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Article
| Open AccessAn 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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Article
| Open AccessComparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human
The evolution of epigenetic regulation of brain development in primates is not well understood. Here, the authors perform a comparative study of epigenetic dynamics of early prefrontal cortex development between human and rhesus macaque, finding divergent regulatory elements that may be related to cognitive capacity.
- Xuelong Yao
- , Zongyang Lu
- & Jiang Liu
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Article
| Open AccessSingle-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification
This study chronicles dynamic gene expression in differentiating spiral ganglion neurons from murine embryonic day 14.5 to postnatal stage, establishes their lineage trajectories, and identifies molecular determinants of cell fate decision.
- Charles Petitpré
- , Louis Faure
- & Francois Lallemend
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Article
| Open AccessDevelopment of visual response selectivity in cortical GABAergic interneurons
Excitatory neurons in the carnivore and primate visual cortex display orientation selectivity arranged in a modular fashion before the onset of visual experience, but the developmental timeline for visual response selectivity of inhibitory neurons is unknown. Using in vivo calcium imaging in ferret visual cortex, the authors show that experience-dependent emergence of orientation selectivity develops in a modular fashion for inhibitory interneurons over the first week of visual experience.
- Jeremy T. Chang
- & David Fitzpatrick
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Matters Arising
| Open AccessComplexity of biological scaling suggests an absence of systematic trade-offs between sensory modalities in Drosophila
- Max S. Farnworth
- & Stephen H. Montgomery
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Article
| Open AccessDissociable multi-scale patterns of development in personalized brain networks
Studies of brain network development typically focus on a single scale. Here, the authors derived personalized functional networks across scales, and find that network development systematically adheres to and strengthens hierarchical cortical organization.
- Adam R. Pines
- , Bart Larsen
- & Theodore D. Satterthwaite
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Article
| Open AccessAstroblastomas 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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Article
| Open AccessImpaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior
Early postnatal interruption of the bidirectional GABA/TNFSF12 signaling between parvalbumin-positive interneurons and oligodendrocyte precursor cells impairs correct prefrontal cortical network activity and social cognitive behavior later in life.
- Li-Pao Fang
- , Na Zhao
- & Xianshu Bai
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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 AccessWhite matter myelination during early infancy is linked to spatial gradients and myelin content at birth
Myelination in early infancy develops at different rates. Here the authors describe this process whereby the back and top of the brain, as well as sections that are least mature at birth develop the fastest.
- Mareike Grotheer
- , Mona Rosenke
- & Kalanit Grill-Spector
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Article
| Open AccessThe 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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Article
| Open AccessTemperature 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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Article
| Open AccessEndosomal 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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Article
| Open AccessIdentification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis
UBE3A gene dysregulation is associated with neurodevelopmental disorders, but predicting the function of UBE3A variants remains difficult. The authors use a high-throughput assay to categorize variants by functional activity, and show that UBE3A hyperactivity increases the risk of neurodevelopmental disease.
- Kellan P. Weston
- , Xiaoyi Gao
- & Jason J. Yi
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Article
| Open AccessDevelopmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
The authors show that mice that mimic the dual genetic-environmental etiology of psychiatric risk have poor lateral entorhinal cortex-dependent recognition memory already at pre-juvenile age and abnormal communication within LECHP-PFC networks throughout development.
- Xiaxia Xu
- , Lingzhen Song
- & Ileana L. Hanganu-Opatz
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Article
| Open AccessA model of tension-induced fiber growth predicts white matter organization during brain folding
Associations have been established between brain folding and white matter connectivity. Here the authors show that axon elongation, in response to mechanical stresses during cortical expansion and folding, may be sufficient to induce tissue remodeling consistent with white matter organization.
- Kara E. Garcia
- , Xiaojie Wang
- & Christopher D. Kroenke
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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 AccessDopamine D2 receptor regulates cortical synaptic pruning in rodents
Synaptic pruning is important during development and synaptic plasticity. Here, the authors show that the dopamine D2 receptor (Drd2) in the anterior cingulate cortex regulates synaptic pruning, affecting LTD and behaviour in transgenic rats.
- Ya-Qiang Zhang
- , Wei-Peng Lin
- & Dong-Min Yin