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      A single cell transcriptome atlas of the developing zebrafish hindbrain

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          ABSTRACT

          Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.

          Abstract

          Summary: A single cell transcriptome at three stages of zebrafish hindbrain development provides a valuable resource for investigations of the patterning of neurogenesis and transition of progenitors to neuronal differentiation.

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          Most cited references83

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          miR-9: a versatile regulator of neurogenesis

          Soon after its discovery, microRNA-9 (miR-9) attracted the attention of neurobiologists, since it is one of the most highly expressed microRNAs in the developing and adult vertebrate brain. Functional analyses in different vertebrate species have revealed a prominent role of this microRNA in balancing proliferation in embryonic neural progenitor populations. Key transcriptional regulators such as FoxG1, Hes1 or Tlx, were identified as direct targets of miR-9, placing it at the core of the gene network controlling the progenitor state. Recent data also suggest that this function could extend to adult neural stem cells. Other studies point to a role of miR-9 in differentiated neurons. Moreover miR-9 has been implicated in human brain pathologies, either displaying a protective role, such as in Progeria, or participating in disease progression in brain cancers. Altogether functional studies highlight a prominent feature of this highly conserved microRNA, its functional versatility, both along its evolutionary history and across cellular contexts.
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            Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

            ABSTRACT The coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate. Progress has been made deciphering the gene regulatory programmes that are responsible for this process; however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days 9.5-13.5. We confirmed that the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, the analysis highlighted a previously underappreciated temporal component to the mechanisms that generate neuronal diversity, and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes. Together, the data offer insight into the mechanisms that are responsible for neuronal specification and provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function and disease.
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              Notch in the vertebrate nervous system: an old dog with new tricks.

              The Notch pathway is prominent among those known to regulate neural development in vertebrates. Notch receptor activation can inhibit neurogenesis, maintain neural progenitor character, and in some contexts promote gliogenesis and drive binary fate choices. Recently, a wave of exciting studies has emerged, which has both solidified previously held assertions and expanded our understanding of Notch function during neurogenesis and in the adult brain. These studies have examined pathway regulators and interactions, as well as pathway dynamics, with respect to both gene expression and cell-cell signaling. Here, focusing primarily on vertebrates, we review the current literature on Notch signaling in the nervous system, and highlight numerous recent studies that have generated interesting and unexpected advances. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists Ltd
                0950-1991
                1477-9129
                15 March 2020
                16 March 2020
                16 March 2020
                : 147
                : 6
                : dev184143
                Affiliations
                [1 ]Neural Development Laboratory, The Francis Crick Institute , 1 Midland Road, London NW1 1AT, UK
                [2 ]Bioinformatics and Biostatistics, The Francis Crick Institute , 1 Midland Road, London NW1 1AT, UK
                Author notes
                [* ]Author for correspondence ( david.wilkinson@ 123456crick.ac.uk )
                Author information
                http://orcid.org/0000-0003-4240-0320
                http://orcid.org/0000-0002-1279-3760
                http://orcid.org/0000-0001-6757-7080
                Article
                DEV184143
                10.1242/dev.184143
                7097387
                32094115
                c8dd346f-c6f6-4dc1-b3fa-b3630ab778cd
                © 2020. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 23 August 2019
                : 11 February 2020
                Funding
                Funded by: Cancer Research UK, http://dx.doi.org/10.13039/501100000289;
                Award ID: FC001217
                Funded by: Medical Research Council, http://dx.doi.org/10.13039/501100000265;
                Award ID: FC001217
                Funded by: Wellcome Trust, http://dx.doi.org/10.13039/100010269;
                Award ID: FC001217
                Categories
                205
                Techniques and Resources

                Developmental biology
                hindbrain segmentation,dorsoventral patterning,neurogenesis,single cell rna sequencing,hindbrain boundary,fgf signalling

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