Apical and basal Ascl1 (Mash1) progenitors in the dorsal neural tube contribute differentially to inhibitory and excitatory neuronal populations in the spinal cord

AbstractThe spinal cord receives input from peripheral sensory neurons and controls motor output by regulating muscle innervating motor neurons. These functions are carried out by neural circuits comprising molecularly and physiologically distinct neuronal subtypes that are generated in a characteristic spatial-temporal arrangement from progenitors in the embryonic neural tube. The systematic mapping of gene expression in mouse embryos has provided insight into the diversity and complexity of cells in the neural tube. For human embryos, however, less information has been available. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions in four human embryos of Carnegie Stages (CS) CS12, CS14, CS17 and CS19 from Gestational Weeks (W) 4-7. In total we recovered the transcriptomes of 71,219 cells. Analysis of progenitor and neuronal populations from the neural tube, as well as cells of the peripheral nervous system, in dorsal root ganglia adjacent to the neural tube, identified dozens of distinct cell types and facilitated the reconstruction of the differentiation pathways of specific neuronal subtypes. Comparison with existing mouse datasets revealed the overall similarity of mouse and human neural tube development while highlighting specific features that differed between species. These data provide a catalogue of gene expression and cell type identity in the developing neural tube that will support future studies of sensory and motor control systems and can be explored at https://shiny.crick.ac.uk/scviewer/neuraltube/.

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FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord

10.1101/690263 ◽

2019 ◽

Author(s):

Abdulmajeed Fahad Alrefaei ◽

Andrea E. Münsterberg ◽

Grant N. Wheeler

Keyword(s):

Spinal Cord ◽

Cell Proliferation ◽

Neural Tube ◽

Spinal Cord Development ◽

Dorsal Neural Tube ◽

Wnt Ligands ◽

Frizzled Receptors ◽

Developmental Contexts ◽

Developing Spinal Cord

AbstractWnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β-catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.

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Single cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human specific features

Development ◽

10.1242/dev.199711 ◽

2021 ◽

Author(s):

Teresa Rayon ◽

Rory J. Maizels ◽

Christopher Barrington ◽

James Briscoe

Keyword(s):

Spinal Cord ◽

Single Cell ◽

Motor Neurons ◽

Neural Tube ◽

Transcriptome Profiling ◽

Cell Types ◽

Human Embryos ◽

Neuronal Populations ◽

Cell Transcriptome ◽

Human Specific

The spinal cord receives input from peripheral sensory neurons and controls motor output by regulating muscle innervating motor neurons. These functions are carried out by neural circuits comprising molecularly distinct neuronal subtypes generated in a characteristic spatial-temporal arrangement from progenitors in the embryonic neural tube. To gain insight into the diversity and complexity of cells in the developing human neural tube we used single cell mRNA sequencing to profile cervical and thoracic regions in four human embryos of Carnegie Stages (CS) CS12, CS14, CS17 and CS19 from Gestational Weeks 4-7. Analysis of progenitor and neuronal populations from the neural tube and dorsal root ganglia identified dozens of distinct cell types and facilitated the reconstruction of the differentiation pathways of specific neuronal subtypes. Comparison with mouse revealed the overall similarity of mammalian neural tube development while highlighting human specific features. These data provide a catalogue of gene expression and cell type identity in the human neural tube that will support future studies of sensory and motor control systems. The data can be explored at https://shiny.crick.ac.uk/scviewer/neuraltube/.

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Faculty Opinions recommendation of Distinct activities of Msx1 and Msx3 in dorsal neural tube development.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017554.203332 ◽

2004 ◽

Author(s):

Chaya Kalcheim

Keyword(s):

Neural Tube ◽

Dorsal Neural Tube ◽

Neural Tube Development

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Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1

Development ◽

10.1242/dev.121.11.3675 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3675-3686 ◽

Cited By ~ 40

Author(s):

H.M. Stern ◽

A.M. Brown ◽

S.D. Hauschka

Keyword(s):

Neural Tube ◽

Muscle Development ◽

Paraxial Mesoderm ◽

Myogenic Response ◽

Dorsal Neural Tube ◽

Ventral Neural Tube ◽

Myogenic Induction ◽

Inductive Activity

Previous studies have demonstrated that the neural tube/notochord complex is required for skeletal muscle development within somites. In order to explore the localization of myogenic inducing signals within the neural tube, dorsal or ventral neural tube halves were cultured in contact with single somites or pieces of segmental plate mesoderm. Somites and segmental plates cultured with the dorsal half of the neural tube exhibited 70% and 85% myogenic response rates, as determined by immunostaining for myosin heavy chain. This response was slightly lower than the 100% response to whole neural tube/notochord, but was much greater than the 30% and 10% myogenic response to ventral neural tube with and without notochord. These results demonstrate that the dorsal neural tube emits a potent myogenic inducing signal which accounts for most of the inductive activity of whole neural tube/notochord. However, a role for ventral neural tube/notochord in somite myogenic induction was clearly evident from the larger number of myogenic cells induced when both dorsal neural tube and ventral neural tube/notochord were present. To address the role of a specific dorsal neural tube factor in somite myogenic induction, we tested the ability of Wnt-1-expressing fibroblasts to promote paraxial mesoderm myogenesis in vitro. We found that cells expressing Wnt-1 induced a small number of somite and segmental plate cells to undergo myogenesis. This finding is consistent with the localized dorsal neural tube inductive activity described above, but since the ventral neural tube/notochord also possesses myogenic inductive capacity yet does not express Wnt-1, additional inductive factors are likely involved.

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Analysis of the development of the nervous system of the zebrafish, Brachydanio rerio

Development ◽

10.1242/dev.19.2.109 ◽

1968 ◽

Vol 19 (2) ◽

pp. 109-119

Author(s):

Judith Shulman Weis

Keyword(s):

Spinal Cord ◽

Nervous System ◽

Neural Crest ◽

Neural Tube ◽

Sympathetic Neurons ◽

Dorsal Surface ◽

Teleost Fishes ◽

Brachydanio Rerio ◽

Solid Structure ◽

Derivatives Of

In teleost fishes, unlike many other vertebrates, the spinal cord originates as a solid structure, the neural keel, which subsequently hollows out. Unlike vertebrates in which the neural tube is formed from neural folds, and where the neural crest arises from wedge-shaped masses of tissue connecting the neural tube to the general ectoderm, teleosts do not possess a clear morphological neural crest. Initially, the dorsal surface of the keel is broadly attached to the ectoderm as described by Shepard (1961). As the neural primordia become larger and more discrete, the region of attachment narrows, and cells become loose (the ‘loose crest stage’). These cells represent the neural crest. Subsequently they begin to migrate and to differentiate into the various derivatives of neural crest. Both sensory and sympathetic neurons arise from neural crest. At the time of their migration the cells are not morphologically distinguishable.

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Role of FGF signalling in neural crest cell migration during early chick embryo development

Zygote ◽

10.1017/s096719941800045x ◽

2018 ◽

Vol 26 (6) ◽

pp. 457-464 ◽

Cited By ~ 1

Author(s):

Xiao-tan Zhang ◽

Guang Wang ◽

Yan Li ◽

Manli Chuai ◽

Kenneth Ka Ho Lee ◽

...

Keyword(s):

Neural Crest ◽

Neural Tube ◽

Neural Crest Cell ◽

Dominant Negative ◽

Neural Tubes ◽

Dorsal Neural Tube ◽

Neural Crest Cell Migration ◽

Fgf Signalling ◽

Crest Cell

SummaryFibroblast growth factor (FGF) signalling acts as one of modulators that control neural crest cell (NCC) migration, but how this is achieved is still unclear. In this study, we investigated the effects of FGF signalling on NCC migration by blocking this process. Constructs that were capable of inducing Sprouty2 (Spry2) or dominant-negative FGFR1 (Dn-FGFR1) expression were transfected into the cells making up the neural tubes. Our results revealed that blocking FGF signalling at stage HH10 (neurulation stage) could enhance NCC migration at both the cranial and trunk levels in the developing embryos. It was established that FGF-mediated NCC migration was not due to altering the expression of N-cadherin in the neural tube. Instead, we determined that cyclin D1 was overexpressed in the cranial and trunk levels when Sprouty2 was upregulated in the dorsal neural tube. These results imply that the cell cycle was a target of FGF signalling through which it regulates NCC migration at the neurulation stage.

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Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration

eLife ◽

10.7554/elife.57779 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Shashank Gandhi ◽

Erica J Hutchins ◽

Krystyna Maruszko ◽

Jong H Park ◽

Matthew Thomson ◽

...

Keyword(s):

Neural Crest ◽

Neural Tube ◽

Neural Crest Cells ◽

Neural Plate ◽

Chromatin Remodeler ◽

Lineage Specification ◽

Dorsal Neural Tube ◽

Neural Crest Development ◽

Neural Plate Border ◽

Canonical Wnt

During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.

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