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

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

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

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

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

The neural crest is an embryonic stem cell population unique to vertebrates1 whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of new cell types and structures such as jaws and peripheral ganglia2. Although jawless vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates3-8. Here, by contrast, we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification through a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine β-hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA sequencing of isolated ammocoete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge the prevailing dogma that posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.

• MeSH
• aorta anatomie a histologie   embryologie   MeSH
• biologická evoluce * MeSH
• biosyntetické dráhy MeSH
• buněčný rodokmen * MeSH
• crista neuralis * cytologie   metabolismus   MeSH
• dopamin-beta-hydroxylasa metabolismus   genetika   MeSH
• embryonální kmenové buňky cytologie   metabolismus   MeSH
• katecholaminy biosyntéza   metabolismus   MeSH
• neurony * cytologie   metabolismus   MeSH
• obratlovci * anatomie a histologie   embryologie   genetika   MeSH
• Petromyzon anatomie a histologie   embryologie   genetika   MeSH
• sympatická ganglia cytologie   metabolismus   MeSH
• sympatický nervový systém * cytologie   fyziologie   MeSH
• tyrosin-3-monooxygenasa metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• dopamin-beta-hydroxylasa MeSH
• katecholaminy MeSH
• tyrosin-3-monooxygenasa 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

BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

• MeSH
• chrupavka abnormality   embryologie   MeSH
• crista neuralis embryologie   metabolismus   MeSH
• forkhead transkripční faktory biosyntéza   genetika   MeSH
• hlavové nervy embryologie   MeSH
• homeodoménové proteiny genetika   MeSH
• krvácení genetika   MeSH
• lebka embryologie   inervace   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• represorové proteiny biosyntéza   genetika   MeSH
• srdce embryologie   MeSH
• transkripční faktor SOX9 biosyntéza   genetika   MeSH
• vrozené srdeční vady embryologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• Foxd3 protein, mouse MeSH Prohlížeč
• homeodoménové proteiny MeSH
• Mrg1 protein, mouse MeSH Prohlížeč
• represorové proteiny MeSH
• Sox9 protein, mouse MeSH Prohlížeč
• transkripční faktor SOX9 MeSH

The colonization of limb buds by neural crest cells was studied in quail-chick chimeras and in chick embryos using HNK-1 and DiI staining and the LD-DOPA reaction. Two populations of neural crest cells were found to colonize the limb bud. They migrate successively and use different routes of migration. The first population migrates within the limb bud subectodermally at stages before the limb is innervated. In the wing bud the migration route is localized postaxially and in the leg bud preaxially. Two cell types were identified differentiating from this first population: melanoblasts and Merkel cells. The second population of crest cells invades the limb bud at a later stage. These cells follow the routes of ingrowing nerves and migrate along a dorsal and a ventral path which correspond to the position of nerves for extensor and flexor muscles. Crest cells were found here also in the absence of nerves. Schwann cells and terminal glial cells develop from this second population of neural crest cells.

• MeSH
• antigeny CD57 MeSH
• CD antigeny metabolismus   MeSH
• chiméra MeSH
• Coturnix MeSH
• crista neuralis cytologie   embryologie   MeSH
• diferenciační antigeny T-lymfocytů metabolismus   MeSH
• dihydroxyfenylalanin metabolismus   MeSH
• fluorescenční barviva MeSH
• imunohistochemie MeSH
• karbocyaniny MeSH
• končetiny embryologie   MeSH
• kuřecí embryo MeSH
• pohyb buněk MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3,3'-dioctadecylindocarbocyanine MeSH Prohlížeč
• antigeny CD57 MeSH
• CD antigeny MeSH
• diferenciační antigeny T-lymfocytů MeSH
• dihydroxyfenylalanin MeSH
• fluorescenční barviva MeSH
• karbocyaniny MeSH

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