neural crest cells
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The cranial neural crest (CNC) arises within the developing central nervous system, but then migrates away from the neural tube in three consecutive streams termed mandibular, hyoid and branchial, respectively, according to the order along the anteroposterior axis. While the process of neural crest emigration generally follows a conserved anterior to posterior sequence across vertebrates, we find that ray-finned fishes (bichir, sterlet, gar, and pike) exhibit several heterochronies in the timing and order of CNC emergence that influences their subsequent migratory patterns. First, emigration of the cranial neural crest in these fishes occurs prematurely compared to other vertebrates, already initiating during early neurulation and well before neural tube closure. Second, delamination of the hyoid stream occurs prior to the more anterior mandibular stream; this is associated with early morphogenesis of key hyoid structures like external gills (bichir), a large opercular flap (gar) or first forming cartilage (pike). In sterlet, the hyoid and branchial CNC cells form a single hyobranchial sheet, which later segregates in concert with second pharyngeal pouch morphogenesis. Taken together, the results show that despite generally conserved migratory patterns, heterochronic alterations in the timing of emigration and pattern of migration of CNC cells accompanies morphological diversity of ray-finned fishes.
- Klíčová slova
- Craniofacial, Evolution, Neural crest, Neurulation, Vertebrates,
- MeSH
- biologická evoluce * MeSH
- crista neuralis cytologie embryologie MeSH
- embryo nesavčí cytologie embryologie MeSH
- pohyb buněk fyziologie MeSH
- ryby embryologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages.
- Klíčová slova
- Schwann cell lineage, Schwann cell precursors, multipotency, neural crest, regulons,
- MeSH
- buněčná diferenciace fyziologie MeSH
- crista neuralis * MeSH
- neurogeneze fyziologie MeSH
- periferní nervy MeSH
- Schwannovy buňky * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Bone is an evolutionary novelty of vertebrates, likely to have first emerged as part of ancestral dermal armor that consisted of osteogenic and odontogenic components. Whether these early vertebrate structures arose from mesoderm or neural crest cells has been a matter of considerable debate. To examine the developmental origin of the bony part of the dermal armor, we have performed in vivo lineage tracing in the sterlet sturgeon, a representative of nonteleost ray-finned fish that has retained an extensive postcranial dermal skeleton. The results definitively show that sterlet trunk neural crest cells give rise to osteoblasts of the scutes. Transcriptional profiling further reveals neural crest gene signature in sterlet scutes as well as bichir scales. Finally, histological and microCT analyses of ray-finned fish dermal armor show that their scales and scutes are formed by bone, dentin, and hypermineralized covering tissues, in various combinations, that resemble those of the first armored vertebrates. Taken together, our results support a primitive skeletogenic role for the neural crest along the entire body axis, that was later progressively restricted to the cranial region during vertebrate evolution. Thus, the neural crest was a crucial evolutionary innovation driving the origin and diversification of dermal armor along the entire body axis.
- Klíčová slova
- neural crest, scales, skeleton, sterlet sturgeon, vertebrate evolution,
- MeSH
- biologická evoluce MeSH
- crista neuralis * MeSH
- lebka MeSH
- obratlovci * genetika MeSH
- osteogeneze MeSH
- ryby MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of Adar1 reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of Adar1 mutant phenotypes. By analyzing RNA-Seq data from the sciatic nerves of mouse pups after conditional neural crest deletion of Adar1 (Adar1cKO), we here identified the transcription factors deregulated in Adar1cKO mutants compared to the controls. Through Adar1;Mavs and Adar1cKO;Egr1 double-mutant mouse rescue analyses, we then highlighted that the aberrant activation of the Mavs adapter protein and overexpression of the early growth response 1 (EGR1) transcription factor contribute to the Adar1 deletion associated defects in Schwann cell development in vivo. In silico and in vitro gene regulation studies additionally suggested that EGR1 might mediate this inhibitory effect through the aberrant regulation of EGR2-regulated myelin genes. We thus demonstrate the role of the Mda5/Mavs pathway, but also that of the Schwann cell transcription factors in Adar1-associated peripheral myelination defects.
- Klíčová slova
- ADAR1, EGR1, MAVS, Schwann cells, differentiation, neural crest,
- MeSH
- adenosindeaminasa * genetika metabolismus MeSH
- buněčná diferenciace * genetika MeSH
- crista neuralis * metabolismus MeSH
- IFIH1 genetika metabolismus MeSH
- myelinová pochva metabolismus MeSH
- myši knockoutované * MeSH
- myši MeSH
- Schwannovy buňky * metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ADAR1 protein, mouse MeSH Prohlížeč
- adenosindeaminasa * MeSH
- Ifih1 protein, mouse MeSH Prohlížeč
- IFIH1 MeSH
Among various strategies employed for spinal cord injury, stem cell therapy is a potential treatment. So far, a variety of stem cells have been evaluated in animal models and humans with spinal cord injury, and epidermal neural crest stem cells represent one of the attractive types in this area. Although these multipotent stem cells have been assessed in several spinal cord injury models by independent laboratories, extensive work remains to be done to ascertain whether these cells can safely improve the outcome following human spinal cord injury. Among the models that closely mimic human spinal cord injury, the in vitro model of injury in organotypic spinal cord slice culture has been identified as one of the faithful platforms for injury-related investigations. In this study, green fluorescent protein-expressing stem cells were grafted into injured organotypic spinal cord slice culture and their survival was examined by confocal microscope seven days after transplantation. Data obtained from this preliminary study showed that these stem cells can survive on top of the surface of injured slices, as observed on day seven following their transplantation. This result revealed that this in vitro model of injury can be considered as a suitable context for further evaluation of epidermal neural crest stem cells before their application in large animals.
- MeSH
- biologické modely MeSH
- buněčná smrt MeSH
- crista neuralis cytologie MeSH
- epidermální buňky * MeSH
- kmenové buňky cytologie MeSH
- kultivované buňky MeSH
- mícha cytologie MeSH
- potkani Wistar MeSH
- transplantace kmenových buněk MeSH
- tvar buňky MeSH
- viabilita buněk MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- zelené fluorescenční proteiny MeSH
Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.
- Klíčová slova
- Early face development, clonal envelopes, embryonic development, migration, morphogenesis, neural crest cells,
- MeSH
- anatomické modely MeSH
- buněčná diferenciace * MeSH
- buněčné klony cytologie MeSH
- crista neuralis cytologie MeSH
- dánio pruhované MeSH
- ektoderm cytologie embryologie MeSH
- exprese genu MeSH
- fenotyp MeSH
- mezoderm cytologie embryologie MeSH
- morfogeneze * MeSH
- myši MeSH
- obličej embryologie MeSH
- organogeneze * MeSH
- pohyb buněk MeSH
- reportérové geny MeSH
- zobrazování trojrozměrné MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Neural crest cells (NCCs) derive early in vertebrate ontogenesis from neural tube as a population of migratory cells with exquisite differentiation potential. Abnormalities in NCC behaviour are cause of debilitating diseases including cancers and a spectrum of neurocristopathies. Thanks to their multilineage differentiation capacity NCCs offer a cell source for regenerative medicine. Both these aspects make NCC biology an important issue to study, which can currently be addressed using methodologies based on pluripotent stem cells. Here we contributed to understanding the biology of human NCCs by refining the protocol for differentiation/propagation of NCClike cells from human embryonic stem cells and by characterizing the molecular and functional phenotype of such cells. Most importantly, we improved formulation of media for NCC culture, we found that poly-L-ornithine combined with fibronectin provide good support for NCC growth, we unravelled the tendency of cultured NCCs to maintain heterogeneity of CD271 expression, and we showed that NCCs derived here possess the capacity to react to BMP4 signals by dramatically up-regulating MSX1, which is linked to odontogenesis.
- MeSH
- adapalen MeSH
- biologické markery metabolismus MeSH
- buněčná diferenciace * účinky léků MeSH
- crista neuralis cytologie účinky léků metabolismus MeSH
- embryonální kmenové buňky cytologie účinky léků metabolismus MeSH
- fenotyp MeSH
- kostní morfogenetický protein 4 farmakologie MeSH
- lidé MeSH
- naftaleny metabolismus MeSH
- polymerázová řetězová reakce MeSH
- průtoková cytometrie MeSH
- transkripční faktor MSX1 metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adapalen MeSH
- biologické markery MeSH
- kostní morfogenetický protein 4 MeSH
- MSX1 protein, human MeSH Prohlížeč
- naftaleny MeSH
- transkripční faktor MSX1 MeSH
The endostyle is an endodermal organ unique to nonvertebrate chordates except for lamprey larvae, where it serves as forerunner to the adult thyroid. Here, we examine whether the acquisition of neural crest in the vertebrate lineage played a role in the elaboration of the endostyle. CM-DiI lineage tracing reveals a neural crest contribution to the endostyle, and CRISPR-Cas9 mutagenesis of key neural crest genes causes endostyle defects including formation of a single rather than bilobed structure. RNA sequencing reveals gene profiles characteristic of embryonic neural crest cells and Schwann cell precursors in the developing endostyle. Contrasting with the prevailing view that the endostyle is an endoderm-derived organ, we propose that the acquisition of the neural crest played a critical step in promoting thyroid evolution from chordate endostyle.
The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using the mouse model, we show here that active repression of Wnt/β-catenin signaling is required for maintenance of neuroepithelial identity in the anterior neural fold and for inhibition of NC induction. Conditional inactivation of Tcf7l1, a transcriptional repressor of Wnt target genes, leads to aberrant activation of Wnt/β-catenin signaling in the anterior neuroectoderm and its conversion into NC. This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient.
- Klíčová slova
- Forebrain, Mouse, Neural crest, Tcf/Lef, Wnt signaling, Zebrafish,
- MeSH
- beta-katenin metabolismus MeSH
- biologické markery metabolismus MeSH
- buněčný rodokmen * MeSH
- crista neuralis cytologie metabolismus MeSH
- dánio pruhované metabolismus MeSH
- defekty neurální trubice metabolismus patologie MeSH
- delece genu MeSH
- fenotyp MeSH
- integrasy metabolismus MeSH
- lidé MeSH
- myši transgenní MeSH
- přední mozek embryologie metabolismus MeSH
- protein 1 podobný transkripčnímu faktoru 7 metabolismus MeSH
- proteiny dánia pruhovaného metabolismus MeSH
- represorové proteiny metabolismus MeSH
- signální dráha Wnt MeSH
- transdiferenciace buněk MeSH
- transkripční faktor AP-2 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- biologické markery MeSH
- Cre recombinase MeSH Prohlížeč
- integrasy MeSH
- protein 1 podobný transkripčnímu faktoru 7 MeSH
- proteiny dánia pruhovaného MeSH
- represorové proteiny MeSH
- Tcf7l1 protein, mouse MeSH Prohlížeč
- tcf7l1a protein, zebrafish MeSH Prohlížeč
- transkripční faktor AP-2 MeSH
The neural crest is unique to vertebrates and has allowed the evolution of their complicated craniofacial structures. During vertebrate evolution, the acquisition of the neural crest must have been accompanied by the emergence of a new gene regulatory network (GRN). Here, to investigate the role of protein evolution in the emergence of the neural crest GRN, we examined the neural crest cell (NCC) differentiation-inducing activity of chordate FoxD genes. Amphioxus and vertebrate (Xenopus) FoxD proteins both exhibited transcriptional repressor activity in Gal4 transactivation assays and bound to similar DNA sequences in vitro. However, whereas vertebrate FoxD3 genes induced the differentiation of ectopic NCCs when overexpressed in chick neural tube, neither amphioxus FoxD nor any other vertebrate FoxD paralogs exhibited this activity. Experiments using chimeric proteins showed that the N-terminal portion of the vertebrate FoxD3 protein is critical to its NCC differentiation-inducing activity. Furthermore, replacement of the N-terminus of amphioxus FoxD with a 39-amino-acid segment from zebrafish FoxD3 conferred neural crest-inducing activity on amphioxus FoxD or zebrafish FoxD1. Therefore, fixation of this N-terminal amino acid sequence may have been crucial in the evolutionary recruitment of FoxD3 to the vertebrate neural crest GRN.
- Klíčová slova
- Amphioxus, FoxD3, Neural crest,
- MeSH
- crista neuralis fyziologie MeSH
- forkhead transkripční faktory chemie genetika fyziologie MeSH
- genetická transkripce MeSH
- klonování DNA MeSH
- obratlovci embryologie MeSH
- represorové proteiny fyziologie MeSH
- vývojová regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
- represorové proteiny MeSH
