Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

Delile, Julien; Rayón, Teresa; Melchionda, Manuela; Edwards, A.; Briscoe, James; Sagner, Andreas

doi:10.1242/dev.173807

Cited by 293 publications

(404 citation statements)

References 74 publications

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“…D-V positional information regulated by BMP, Wnt and Shh signalling is a key feature of the developing neuroepithelium that underlies specification of neuronal cell types. Extensive molecular characterisation has been carried out in the spinal cord (Delile et al, 2019;Gouti et al, 2015), but less widely for the hindbrain. At all stages analysed, progenitors were clustered based on their D-V identity, reflecting that D-V patterning is established early and maintained during hindbrain neurogenesis.…”

Section: Dorsoventral Signatures Of Progenitors and Differentiating Nmentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

2020

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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.

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Section: Dorsoventral Signatures Of Progenitors and Differentiating Nmentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

2020

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“…Dorsoventral positional information is a key feature of the developing neural epithelium that underlies specification of neuronal cell types. Extensive molecular characterization has been carried out in the spinal cord (Delile et al, 2019; Gouti et al, 2015), but less widely for the hindbrain. At all stages analysed, progenitors were clustered based on their dorsoventral identity, reflecting that D-V patterning is established early and maintained during hindbrain neurogenesis.…”

Section: Resultsmentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

Tambalo

Mitter

Wilkinson

2019

Preprint

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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 bounderies and segment centres, in part mediated by Fgf20 signaling. 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.

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“…Irrespective, it is clear lampreys do have more copies in many transcription factor gene families than amphioxus or sea squirts. Many of the jawed vertebrate paralogues are expressed by different cell populations in the spinal cord (Figure and Table ), as assessed by in situ hybridization (summarized by Reference ) and more recently by single‐cell sequencing . Some of this could represent subfunctionalization of original broader expression patterns into subdomains, however some must also be neofunctionalization and/or specialization, for example, the paralogues Nkx6.1 and Nkx6.2 , and Dbx1 and Dbx2 , overlap but are functionally distinct, setting up the interneuron progenitor zones p0, p1, and p2 .…”

Section: A Role For Gene Duplication In Spinal Cord Evolutionmentioning

confidence: 99%

Evolution of vertebrate spinal cord patterning

Leung

Shimeld

2019

Developmental Dynamics

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The vertebrate spinal cord is organized across three developmental axes, anterior‐posterior (AP), dorsal‐ventral (DV), and medial‐lateral (ML). Patterning of these axes is regulated by canonical intercellular signaling pathways: the AP axis by Wnt, fibroblast growth factor, and retinoic acid (RA), the DV axis by Hedgehog, Tgfβ, and Wnt, and the ML axis where proliferation is controlled by Notch. Developmental time plays an important role in which signal does what and when. Patterning across the three axes is not independent, but linked by interactions between signaling pathway components and their transcriptional targets. Combined this builds a sophisticated organ with many different types of cell in specific AP, DV, and ML positions. Two living lineages share phylum Chordata with vertebrates, amphioxus, and tunicates, while the jawless fish such as lampreys, survive as the most basally divergent vertebrate lineage. Genes and mechanisms shared between lampreys and other vertebrates tell us what predated vertebrates, while those also shared with other chordates tell us what evolved early in chordate evolution. Between these lie vertebrate innovations: genetic and developmental changes linked to evolution of new morphology. These include gene duplications, differences in how signals are received, and new regulatory connections between signaling pathways and their target genes.

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Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

Cited by 293 publications

References 74 publications

A single cell transcriptome atlas of the developing zebrafish hindbrain

A single cell transcriptome atlas of the developing zebrafish hindbrain

A single cell transcriptome atlas of the developing zebrafish hindbrain

Evolution of vertebrate spinal cord patterning

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