Abstract:The neural crest is a unique population of multipotent cells forming in vertebrate embryos. Their vast cell fate potential enables the generation of a diverse array of differentiated cell types
in vivo
. These include, among others, connective tissue, cartilage and bone of the face and skull, neurons and glia of the peripheral nervous system (including enteric nervous system), and melanocytes. Following migration, these derivatives extensively populate multiple germ layers. Within the co… Show more
“…However, despite advances in our knowledge of the mechanisms that control early CNCC fate decisions, limited information is available about how postmigratory CNCCs acquire cell-fate-specific programs 10 . Furthermore, the GRNs of postmigratory CNCCs at the single-cell level remain largely unknown 11 .…”
Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern the cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Using the mouse molar as a model, we perform single-cell transcriptome profiling to interrogate the cell fate diversification of postmigratory cranial neural crest cells. We reveal the landscape of transcriptional heterogeneity and define the specific cellular domains during the progression of cranial neural crest cell-derived dental lineage diversification, and find that each domain makes a specific contribution to distinct molar mesenchymal tissues. Furthermore, IGF signaling-mediated cell-cell interaction between the cellular domains highlights the pivotal role of autonomous regulation of the dental mesenchyme. Importantly, we reveal cell-type-specific gene regulatory networks in the dental mesenchyme and show that Foxp4 is indispensable for the differentiation of periodontal ligament. Our single-cell atlas provides comprehensive mechanistic insight into the cell fate diversification process of the cranial neural crest cell-derived odontogenic populations.
“…However, despite advances in our knowledge of the mechanisms that control early CNCC fate decisions, limited information is available about how postmigratory CNCCs acquire cell-fate-specific programs 10 . Furthermore, the GRNs of postmigratory CNCCs at the single-cell level remain largely unknown 11 .…”
Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern the cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Using the mouse molar as a model, we perform single-cell transcriptome profiling to interrogate the cell fate diversification of postmigratory cranial neural crest cells. We reveal the landscape of transcriptional heterogeneity and define the specific cellular domains during the progression of cranial neural crest cell-derived dental lineage diversification, and find that each domain makes a specific contribution to distinct molar mesenchymal tissues. Furthermore, IGF signaling-mediated cell-cell interaction between the cellular domains highlights the pivotal role of autonomous regulation of the dental mesenchyme. Importantly, we reveal cell-type-specific gene regulatory networks in the dental mesenchyme and show that Foxp4 is indispensable for the differentiation of periodontal ligament. Our single-cell atlas provides comprehensive mechanistic insight into the cell fate diversification process of the cranial neural crest cell-derived odontogenic populations.
“…With these studies, the once simple model of morphogens driving transcriptional regulator expression in NCCs has become more complex, suggesting waves of signaling rather than finite signals. More information on the roles of signaling pathways in NCC development can be found in detailed reviews ( Artinger and Monsoro-Burq, 2021 ; Rogers et al, 2012 ; Rogers and Nie, 2018 ; Williams and Bohnsack, 2019 ).…”
Section: Classical Factors In Ncc Formation and Emtmentioning
Neural crest cells (NCCs) are a dynamic, multipotent, vertebrate-specific population of embryonic stem cells. These ectodermally-derived cells contribute to diverse tissue types in developing embryos including craniofacial bone and cartilage, the peripheral and enteric nervous systems and pigment cells, among a host of other cell types. Due to their contribution to a significant number of adult tissue types, the mechanisms that drive their formation, migration and differentiation are highly studied. NCCs have a unique ability to transition from tightly adherent epithelial cells to mesenchymal and migratory cells by altering their polarity, expression of cell-cell adhesion molecules and gaining invasive abilities. In this Review, we discuss classical and emerging factors driving NCC epithelial-to-mesenchymal transition and migration, highlighting the role of signaling and transcription factors, as well as novel modifying factors including chromatin remodelers, small RNAs and post-translational regulators, which control the availability and longevity of major NCC players.
“…We tested it on another vertebrate organism, zebrafish, to evaluate its accuracy for NC annotation. Our binary classifier determined whether a cell was NC or not, using our annotated frog whole embryo dataset at seven developmental stages (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The algorithm was tested on a zebrafish whole embryo SC dataset (21) at stage 14hpf (equivalent to frog stage 22) with a result of 0.95 for AUC score and 0.66 for F1 score (F1 score defines the weighted harmonic mean of the precision and recall, and it is equal to 0.05 for a random model applied to the zebrafish dataset, Fig.…”
Section: General Strategy For Identification Of Neural Crest and Neur...mentioning
confidence: 99%
“…During gastrulation (stages [11][12][13], the neural plate and the neural border zone are induced from the dorsal ectoderm due to BMP antagonists in the midline and Wnt/FGF signaling from the underlying mesoderm (18). As early as stage 10.5-11, the neural border initiates a few distinct gene expressions, such as pax3/7 (19).…”
Section: General Strategy For Identification Of Neural Crest and Neur...mentioning
confidence: 99%
“…at the neural border) would define the developmental genetic trajectories of the complete NC lineage tree. Most of the recent SC studies on NC cells have mainly explored NC after emigration (Artinger and Monsoro-Burq, 2021; Supplementary File 1 - Table S1). In contrast, pre-migratory NC single cells have received limited exploration, mostly around the EMT stage and on small cell numbers at a specific level of the body axis (Ling and Sauka-Spengler, 2019; Zalc et al, 2021).…”
Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning and large-scale experimental validation to provide a comprehensive GRN underlying neural crest fate diversification from induction to early migration stages. During gastrulation, a transient neural border zone state precedes choice between neural crest and placodes following a "dual convergence model". Transcription factor connectome and bifurcation analyses demonstrate the early emergence of neural crest fates at neural plate stage, alongside an unbiased multipotent lineage persisting until after epithelial-mesenchymal transition. We decipher the circuits driving cranial and vagal neural crest formation and provide a broadly applicable strategy for investigating SC transcriptomes in vertebrate GRNs in development, evolution and disease.
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