725 results match your criteria: "Centre for Developmental Neurobiology[Affiliation]"

Summary: EpiCompare combines a variety of downstream analysis tools to compare, quality control and benchmark different epigenomic datasets. The package requires minimal input from users, can be run with just one line of code and provides all results of the analysis in a single interactive HTML report. EpiCompare thus enables downstream analysis of multiple epigenomic datasets in a simple, effective and user-friendly manner.

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A revised terminology for the pharyngeal arches and the arch arteries.

J Anat

October 2023

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Centre for Life, Newcastle, UK.

The pharyngeal arches are a series of bulges found on the lateral surface of the head of vertebrate embryos. In humans, and other amniotes, there are five pharyngeal arches and traditionally these have been labelled from cranial to caudal-1, 2, 3, 4 and 6. This numbering is odd-there is no '5'.

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The single-cell and spatial transcriptional landscape of human gastrulation and early brain development.

Cell Stem Cell

June 2023

State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China; Guangdong Institute of Intelligence Science and Technology, Guangdong 519031, China; Changping Laboratory, Beijing 102206, China; New Cornerstone Science Laboratory, Beijing Normal University, Beijing 100875, China. Electronic address:

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia.

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Understanding Glaucoma One Synapse at a Time.

eNeuro

May 2023

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, United Kingdom

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Most adult hippocampal neural stem cells (NSCs) remain quiescent, with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger the transition from quiescence to activation are still poorly understood. Here, we found the activity of the transcriptional co-activator Yap1 to be enriched in active NSCs.

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Multi-synaptic boutons are a feature of CA1 hippocampal connections in the stratum oriens.

Cell Rep

May 2023

MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK. Electronic address:

Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block-face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitatory synapses in the stratum oriens involved multi-synaptic boutons (MSBs), where a single presynaptic bouton containing multiple active zones contacted many postsynaptic spines (from 2 to 7) on the basal dendrites of different cells.

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Critical period-like plasticity (iPlasticity) can be reinstated in the adult brain by several interventions, including drugs and optogenetic modifications. We have demonstrated that a combination of iPlasticity with optimal training improves behaviors related to neuropsychiatric disorders. In this context, the activation of TrkB, a receptor for BDNF, in Parvalbumin-positive (PV) interneurons has a pivotal role in cortical network changes.

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Complex organ formation requires the coordinated morphogenesis of adjacent tissue layers. Here, we report a role for the planar cell polarity (PCP) proteins Fz6 and Celsr1 in generating squamous basal cells in the later stage embryonic epidermis of the mouse is reported, which may impact upon the shape of overlying suprabasal cells. The depth of the epidermis and basal layer as well as cell proliferation index was scored from immunostained wax sections taken from different mouse embryos mutant in planar cell polarity signalling and their wild-type littermates.

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Human neuromuscular diseases represent a diverse group of disorders with unmet clinical need, ranging from muscular dystrophies, such as Duchenne muscular dystrophy (DMD), to neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). In many of these conditions, axonal and neuromuscular synapse dysfunction have been implicated as crucial pathological events, highlighting the need for in vitro disease models that accurately recapitulate these aspects of human neuromuscular physiology. The protocol reported here describes the co-culture of neural spheroids composed of human pluripotent stem cell (PSC)-derived motor neurons and astrocytes, and human PSC-derived myofibers in 3D compartmentalised microdevices to generate functional human neuromuscular circuits in vitro.

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Chandelier cells shine a light on the formation of GABAergic synapses.

Curr Opin Neurobiol

June 2023

Centre for Developmental Neurobiology and MRC Centre for Neurodevelopmental Disorders, King's College London, New Hunt's House, Guy's Hospital Campus, London, SE1 1UL, London, UK. Electronic address:

Uncovering the wiring rules employed by neurons during development represents a formidable challenge with important repercussions for neurodevelopmental disorders. Chandelier cells (ChCs) are a singular GABAergic interneuron type, with a unique morphology, that have recently begun to shed light on the rules that drive the formation and plasticity of inhibitory synapses. This review will focus on the wealth of recent data charting the emergence of synapses formed by ChCs onto pyramidal cells, from the molecules involved to the plasticity of these connections during development.

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The pharyngeal arches are a series of bulges on the lateral surface of the embryonic head. They are a defining feature of the most conserved, the phylotypic, stage of vertebrate development. In many vertebrate clades, the segmental arrangement of the pharyngeal arches is translated into the iterative anatomy of the gill arches.

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Enrichment of human embryonic stem cell-derived V3 interneurons using an Nkx2-2 gene-specific reporter.

Sci Rep

February 2023

Centre for Gene Therapy and Regenerative Medicine, Centre for Developmental Neurobiology, MRC Centre for Neurodevelopmental Disorders, King's College London, 28th Floor Tower Wing, Guy's Campus, Great Maze Pond, London, SE1 9RT, UK.

V3 spinal interneurons are a key element of the spinal circuits, which control motor function. However, to date, there are no effective ways of deriving a pure V3 population from human pluripotent stem cells. Here, we report a method for differentiation and isolation of spinal V3 interneurons, combining extrinsic factor-mediated differentiation and magnetic activated cell sorting.

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Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection.

Brain

March 2023

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Maternal viral infection and immune response are known to increase the risk of altered development of the foetal brain. Given the ongoing global pandemic of coronavirus disease 2019 (COVID-19), investigating the impact of SARS-CoV-2 on foetal brain health is of critical importance. Here, we report the presence of SARS-CoV-2 in first and second trimester foetal brain tissue in association with cortical haemorrhages.

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Many spliceosomal introns are excised from nascent transcripts emerging from RNA polymerase II (RNA Pol II). The extent of cell-type-specific regulation and possible functions of such co-transcriptional events remain poorly understood. We examined the role of the RNA-binding protein PTBP1 in this process using an acute depletion approach followed by the analysis of chromatin- and RNA Pol II-associated transcripts.

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Topographically Localized Modulation of Tectal Cell Spatial Tuning by Complex Natural Scenes.

eNeuro

January 2023

The Centre for Developmental Neurobiology and MRC Center for Neurodevelopmental Disorders, King's College London, London, United Kingdom, SE1 1UL.

The tuning properties of neurons in the visual system can be contextually modulated by the statistics of the area surrounding their receptive field (RF), particularly when the surround contains natural features. However, stimuli presented in specific egocentric locations may have greater behavioral relevance, raising the possibility that the extent of contextual modulation may vary with position in visual space. To explore this possibility, we utilized the small size and optical transparency of the larval zebrafish to describe the form and spatial arrangement of contextually modulated cells throughout an entire tectal hemisphere.

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The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. , Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells.

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Rapid presynaptic maturation in naturally regenerating axons of the adult mouse olfactory nerve.

Cell Rep

December 2022

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK. Electronic address:

Successful neuronal regeneration requires the reestablishment of synaptic connectivity. This process requires the reconstitution of presynaptic neurotransmitter release, which we investigate here in a model of entirely natural regeneration. After toxin-induced injury, olfactory sensory neurons in the adult mouse olfactory epithelium can regenerate fully, sending axons via the olfactory nerve to reestablish synaptic contact with postsynaptic partners in the olfactory bulb.

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Cortical wiring by synapse type-specific control of local protein synthesis.

Science

November 2022

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK.

Article Synopsis
  • Neurons rely on local protein synthesis to maintain their complex structure, particularly at individual synapses.
  • Researchers discovered a signaling pathway that controls the local production of proteins necessary for forming excitatory synapses on specific interneurons in the mouse brain.
  • This pathway involves the regulation of Tsc2 by ErbB4, which helps tailor mRNA translation to specific cell and synapse types, demonstrating how local protein synthesis is crucial for synapse formation in the nervous system.
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Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.

Nat Commun

November 2022

Centre for Developmental Neurobiology and Medical Research Council Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, Guy's Campus, King's College London, London, SE1 1UL, UK.

Loss of SFPQ is a hallmark of motor degeneration in ALS and prevents maturation of motor neurons when occurring during embryogenesis. Here, we show that in zebrafish, developing motor neurons lacking SFPQ exhibit axon extension, branching and synaptogenesis defects, prior to degeneration. Subcellular transcriptomics reveals that loss of SFPQ in neurons produces a complex set of aberrant intron-retaining (IR) transcripts coding for neuron-specific proteins that accumulate in neurites.

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Synaptic specificity during neurodevelopment is driven by combinatorial interactions between select cell adhesion molecules expressed at the synaptic membrane. These protein-protein interactions are important for instructing the correct connectivity and functionality of the nervous system. Teneurins are one family of synaptic adhesion molecules, highly conserved and widely expressed across interconnected areas during development.

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Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression in response to physiological cues. Although most of the pre-mRNA processing is thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a component of the major spliceosome, localizes in RNA-associated granules in zebrafish axons.

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Adaptive sensory behavior is thought to depend on processing in recurrent cortical circuits, but how dynamics in these circuits shapes the integration and transmission of sensory information is not well understood. Here, we study neural coding in recurrently connected networks of neurons driven by sensory input. We show analytically how information available in the network output varies with the alignment between feedforward input and the integrating modes of the circuit dynamics.

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