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1.
Development ; 151(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958074

RESUMO

The bromodomain and extra-terminal (BET) family of proteins reads epigenetic histone acetylation marks on the genome and regulates the transcriptional machinery. In their study, Carole LaBonne and colleagues reveal the role of BET protein activity in the maintenance of pluripotency and establishment of the neural crest in Xenopus laevis. To know more about their work, we spoke to the first author Paul Huber and the corresponding author Carole LaBonne, Developmental and Stem Cell Biologist at Northwestern University.


Assuntos
Xenopus laevis , Animais , História do Século XXI , Humanos , História do Século XX , Crista Neural/metabolismo , Biologia do Desenvolvimento/história
2.
Nat Commun ; 15(1): 4632, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951500

RESUMO

ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-ß in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.


Assuntos
Cardiopatias Congênitas , Coração , Camundongos Knockout , Crista Neural , Proteínas Repressoras , Animais , Crista Neural/metabolismo , Crista Neural/embriologia , Camundongos , Coração/embriologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Regulação da Expressão Gênica no Desenvolvimento , Cromatina/metabolismo , Transdução de Sinais , Miocárdio/metabolismo , Feminino
3.
PLoS One ; 19(6): e0304557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38941348

RESUMO

Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial neural crest cells (CNCs) that form facial bones and cartilage. We previously reported that PAE rapidly represses expression of >70 ribosomal proteins (padj = 10-E47). Ribosome dysbiogenesis causes nucleolar stress and activates p53-MDM2-mediated apoptosis. Using primary avian CNCs and the murine CNC line O9-1, we tested whether nucleolar stress and p53-MDM2 signaling mediates this apoptosis. We further tested whether haploinsufficiency in genes that govern ribosome biogenesis, using a blocking morpholino approach, synergizes with alcohol to worsen craniofacial outcomes in a zebrafish model. In both avian and murine CNCs, pharmacologically relevant alcohol exposure (20mM, 2hr) causes the dissolution of nucleolar structures and the loss of rRNA synthesis; this nucleolar stress persisted for 18-24hr. This was followed by reduced proliferation, stabilization of nuclear p53, and apoptosis that was prevented by overexpression of MDM2 or dominant-negative p53. In zebrafish embryos, low-dose alcohol or morpholinos directed against ribosomal proteins Rpl5a, Rpl11, and Rps3a, the Tcof homolog Nolc1, or mdm2 separately caused modest craniofacial malformations, whereas these blocking morpholinos synergized with low-dose alcohol to reduce and even eliminate facial elements. Similar results were obtained using a small molecule inhibitor of RNA Polymerase 1, CX5461, whereas p53-blocking morpholinos normalized craniofacial outcomes under high-dose alcohol. Transcriptome analysis affirmed that alcohol suppressed the expression of >150 genes essential for ribosome biogenesis. We conclude that alcohol causes the apoptosis of CNCs, at least in part, by suppressing ribosome biogenesis and invoking a nucleolar stress that initiates their p53-MDM2 mediated apoptosis. We further note that the facial deficits that typify PAE and some ribosomopathies share features including reduced philtrum, upper lip, and epicanthal distance, suggesting the facial deficits of PAE represent, in part, a ribosomopathy.


Assuntos
Apoptose , Etanol , Crista Neural , Ribossomos , Proteína Supressora de Tumor p53 , Peixe-Zebra , Animais , Crista Neural/metabolismo , Crista Neural/efeitos dos fármacos , Ribossomos/metabolismo , Ribossomos/efeitos dos fármacos , Etanol/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Apoptose/efeitos dos fármacos , Camundongos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Nucléolo Celular/metabolismo , Nucléolo Celular/efeitos dos fármacos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Crânio/patologia , Crânio/metabolismo , Crânio/efeitos dos fármacos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
4.
Mol Cells ; 47(6): 100076, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825188

RESUMO

The actin-based cytoskeleton is considered a fundamental driving force for cell differentiation and development. Destrin (Dstn), a member of the actin-depolymerizing factor family, regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of dstn have yet to be fully elucidated. Here, we investigated the physiological functions of dstn during early embryonic development using Xenopus laevis as an experimental model organism. dstn is expressed in anterior neural tissue and neural plate during Xenopus embryogenesis. Depleting dstn promoted morphants with short body axes and small heads. Moreover, dstn inhibition extended the neural plate region, impairing cell migration and distribution during neurulation. In addition to the neural plate, dstn knockdown perturbed neural crest cell migration. Our data suggest new insights for understanding the roles of actin dynamics in embryonic neural development, simultaneously presenting a new challenge for studying the complex networks governing cell migration involving actin dynamics.


Assuntos
Movimento Celular , Destrina , Desenvolvimento Embrionário , Xenopus laevis , Animais , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Destrina/metabolismo , Destrina/genética , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Crista Neural/metabolismo , Crista Neural/embriologia , Crista Neural/citologia , Neurogênese , Placa Neural/metabolismo , Placa Neural/embriologia , Actinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento
5.
Development ; 151(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38884356

RESUMO

Neural crest cells are a stem cell population unique to vertebrate embryos that retains broad multi-germ layer developmental potential through neurulation. Much remains to be learned about the genetic and epigenetic mechanisms that control the potency of neural crest cells. Here, we examine the role that epigenetic readers of the BET (bromodomain and extra terminal) family play in controlling the potential of pluripotent blastula and neural crest cells. We find that inhibiting BET activity leads to loss of pluripotency at blastula stages and a loss of neural crest at neurula stages. We compare the effects of HDAC (an eraser of acetylation marks) and BET (a reader of acetylation) inhibition and find that they lead to similar cellular outcomes through distinct effects on the transcriptome. Interestingly, loss of BET activity in cells undergoing lineage restriction is coupled to increased expression of genes linked to pluripotency and prolongs the competence of initially pluripotent cells to transit to a neural progenitor state. Together these findings advance our understanding of the epigenetic control of pluripotency and the formation of the vertebrate neural crest.


Assuntos
Crista Neural , Animais , Crista Neural/citologia , Crista Neural/metabolismo , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Xenopus laevis/embriologia , Blástula/metabolismo , Blástula/citologia , Diferenciação Celular , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Transcriptoma/genética
6.
Sci Adv ; 10(25): eado1583, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905335

RESUMO

Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest-enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neuroblastoma , Peixe-Zebra , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Linhagem da Célula/genética , Crista Neural/metabolismo , Crista Neural/patologia , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patologia , Peixe-Zebra/genética
7.
J Neurosci ; 44(28)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38830761

RESUMO

The vagal ganglia, comprised of the superior (jugular) and inferior (nodose) ganglia of the vagus nerve, receive somatosensory information from the head and neck or viscerosensory information from the inner organs, respectively. Developmentally, the cranial neural crest gives rise to all vagal glial cells and to neurons of the jugular ganglia, while the epibranchial placode gives rise to neurons of the nodose ganglia. Crest-derived nodose glial progenitors can additionally generate autonomic neurons in the peripheral nervous system, but how these progenitors generate neurons is unknown. Here, we found that some Sox10+ neural crest-derived cells in, and surrounding, the nodose ganglion transiently expressed Phox2b, a master regulator of autonomic nervous system development, during early embryonic life. Our genetic lineage-tracing analysis in mice of either sex revealed that despite their common developmental origin and extreme spatial proximity, a substantial proportion of glial cells in the nodose, but not in the neighboring jugular ganglia, have a history of Phox2b expression. We used single-cell RNA-sequencing to demonstrate that these progenitors give rise to all major glial subtypes in the nodose ganglia, including Schwann cells, satellite glia, and glial precursors, and mapped their spatial distribution by in situ hybridization. Lastly, integration analysis revealed transcriptomic similarities between nodose and dorsal root ganglia glial subtypes and revealed immature nodose glial subtypes. Our work demonstrates that these crest-derived nodose glial progenitors transiently express Phox2b, give rise to the entire complement of nodose glial cells, and display a transcriptional program that may underlie their bipotent nature.


Assuntos
Proteínas de Homeodomínio , Crista Neural , Neuroglia , Gânglio Nodoso , Fatores de Transcrição , Animais , Gânglio Nodoso/citologia , Gânglio Nodoso/metabolismo , Camundongos , Neuroglia/metabolismo , Neuroglia/citologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Crista Neural/citologia , Crista Neural/metabolismo , Feminino , Masculino , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Camundongos Endogâmicos C57BL
8.
Elife ; 132024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873887

RESUMO

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker Dlc1 in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.


Assuntos
Transição Epitelial-Mesenquimal , Crista Neural , Crista Neural/citologia , Animais , Camundongos , Análise de Célula Única
9.
Adv Exp Med Biol ; 1441: 125-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884708

RESUMO

This chapter discusses the role of cardiac neural crest cells in the formation of the septum that divides the cardiac arterial pole into separate systemic and pulmonary arteries. Further, cardiac neural crest cells directly support the normal development and patterning of derivatives of the caudal pharyngeal arches, including the great arteries, thymus, thyroid, and parathyroids. Recently, cardiac neural crest cells have also been shown to indirectly influence the development of the secondary heart field, another derivative of the caudal pharynx, by modulating signaling in the pharynx. The contribution and function of the cardiac neural crest cells has been learned in avian models; most of the genes associated with cardiac neural crest function have been identified using mouse models. Together these studies show that the neural crest cells may not only critical for normal cardiovascular development but also may be involved secondarily because they represent a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Cardiac neural crest cells span from the caudal pharynx into the outflow tract, and therefore may be susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations resulting from genetic and/or environmental insults necessarily requires better understanding the role of cardiac neural crest cells in cardiac development.


Assuntos
Crista Neural , Crista Neural/embriologia , Crista Neural/citologia , Crista Neural/metabolismo , Animais , Humanos , Coração/embriologia , Camundongos
10.
Adv Exp Med Biol ; 1441: 645-659, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884739

RESUMO

Tetralogy of Fallot and double-outlet right ventricle are outflow tract (OFT) alignment defects situated on a continuous disease spectrum. A myriad of upstream causes can impact on ventriculoarterial alignment that can be summarized as defects in either i) OFT elongation during looping morphogenesis or ii) OFT remodeling during cardiac septation. Embryological processes underlying these two developmental steps include deployment of second heart field cardiac progenitor cells, establishment and transmission of embryonic left/right information driving OFT rotation and OFT cushion and valve morphogenesis. The formation and remodeling of pulmonary trunk infundibular myocardium is a critical component of both steps. Defects in myocardial, endocardial, or neural crest cell lineages can result in alignment defects, reflecting the complex intercellular signaling events that coordinate arterial pole development. Importantly, however, OFT alignment is mechanistically distinct from neural crest-driven OFT septation, although neural crest cells impact indirectly on alignment through their role in modulating signaling during SHF development. As yet poorly understood nongenetic causes of alignment defects that impact the above processes include hemodynamic changes, maternal exposure to environmental teratogens, and stochastic events. The heterogeneity of causes converging on alignment defects characterizes the OFT as a hotspot of congenital heart defects.


Assuntos
Modelos Animais de Doenças , Dupla Via de Saída do Ventrículo Direito , Transdução de Sinais , Tetralogia de Fallot , Tetralogia de Fallot/genética , Tetralogia de Fallot/patologia , Tetralogia de Fallot/fisiopatologia , Tetralogia de Fallot/embriologia , Animais , Dupla Via de Saída do Ventrículo Direito/genética , Dupla Via de Saída do Ventrículo Direito/patologia , Dupla Via de Saída do Ventrículo Direito/fisiopatologia , Humanos , Crista Neural/metabolismo , Crista Neural/patologia , Crista Neural/embriologia , Morfogênese/genética
11.
J Vis Exp ; (207)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829111

RESUMO

The human enteric nervous system, ENS, is a large network of glial and neuronal cell types with remarkable neurotransmitter diversity. The ENS controls bowel motility, enzyme secretion, and nutrient absorption and interacts with the immune system and the gut microbiome. Consequently, developmental and acquired defects of the ENS are responsible for many human diseases and may contribute to symptoms of Parkinson's disease. Limitations in animal model systems and access to primary tissue pose significant experimental challenges in studies of the human ENS. Here, a detailed protocol is presented for effective in vitro derivation of the ENS lineages from human pluripotent stem cells, hPSC, using defined culture conditions. Our protocol begins with directed differentiation of hPSCs to enteric neural crest cells within 15 days and yields diverse subtypes of functional enteric neurons within 30 days. This platform provides a scalable resource for developmental studies, disease modeling, drug discovery, and regenerative applications.


Assuntos
Diferenciação Celular , Sistema Nervoso Entérico , Crista Neural , Células-Tronco Pluripotentes , Humanos , Sistema Nervoso Entérico/citologia , Células-Tronco Pluripotentes/citologia , Diferenciação Celular/fisiologia , Crista Neural/citologia , Técnicas Citológicas/métodos , Neurônios/citologia
12.
Biol Open ; 13(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38874999

RESUMO

The neural crest (NC) is an embryonic multipotent and transitory population of cells that appears during late gastrulation/early neurulation in the developing embryos of vertebrate organisms. Often called "the fourth germ layer", the NC is characterised by incredible mobility, which allows the NC cells to migrate throughout the whole embryo, giving rise to an astonishing number of different derivatives in the adult organism, such as craniofacial skeleton, adrenal gland, enteric nervous system and melanocytes. Because of these properties, neurocristopathies (NCPs), which is the term used to classify genetic diseases associated with NC developmental defects, are often syndromic and, taken all together, are the most common type of genetic disease. The NEUcrest consortium is an EU funded innovative training network (ITN) that aims to study the NC and NCPs. In March 2024, the early stage researchers (ESRs) in the NEUcrest consortium organised an in-person conference for well-established and early career researchers to discuss new advances in the NC and NCPs field, starting from the induction of the NC, and then moving on to migration and differentiation processes they undergo. The conference focused heavily on NCPs associated with each of these steps. The conference also included events, such as a round table to discuss the future of the NC research, plus a talk by a person living with an NCP. This 3-day conference aimed to bring together the past, present and future of this field to try and unravel the mysteries of this unique cell population.


Assuntos
Crista Neural , Crista Neural/citologia , Crista Neural/embriologia , Humanos , Animais , Diferenciação Celular , Movimento Celular
13.
Nat Commun ; 15(1): 3745, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702304

RESUMO

Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.


Assuntos
Diferenciação Celular , Variações do Número de Cópias de DNA , Proteína Proto-Oncogênica N-Myc , Crista Neural , Neuroblastoma , Humanos , Neuroblastoma/genética , Neuroblastoma/patologia , Crista Neural/metabolismo , Crista Neural/patologia , Feminino , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Aberrações Cromossômicas , Células-Tronco Embrionárias Humanas/metabolismo , Transcriptoma , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
14.
PLoS One ; 19(5): e0303914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809858

RESUMO

The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to the absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an in vivo F0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in the neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.


Assuntos
Sistemas CRISPR-Cas , Sistema Nervoso Entérico , Peixe-Zebra , Animais , Sistema Nervoso Entérico/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Crista Neural/metabolismo , Doença de Hirschsprung/genética
15.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731925

RESUMO

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.


Assuntos
Síndrome de Goldenhar , Peixe-Zebra , Animais , Peixe-Zebra/genética , Humanos , Masculino , Feminino , Síndrome de Goldenhar/genética , Síndrome de Goldenhar/patologia , Apoptose/genética , Crista Neural/metabolismo , Sequenciamento do Exoma , Proliferação de Células/genética , Fenótipo , Mutação , Técnicas de Inativação de Genes
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 758-760, 2024 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-38818565

RESUMO

Char syndrome is a rare autosomal dominant genetic disorder characterized by patent ductus arteriosus, facial dysmorphism, and dysplasia of fingers/toes. It may also be associated with multiple papillae, dental dysplasia, and sleep disorders. TFAP2B has proven to be a pathogenic gene for neural crest derivation and development, and several variants of this gene have been identified. Bone morphogenetic protein signaling plays an important role in embryonic development by participating in limb growth and patterning, and regulation of neural crest cell development. TFAP2B is an upstream regulatory gene for bone morphogenetic proteins 2 and 4. Variants of the TFAP2B gene may lead to abnormal proliferation of neural crest cells by affecting the expression of bone morphogenetic proteins, resulting in multiple organ dysplasia syndrome. In addition, TFAP2B variants may only lead to patent ductus arteriosus instead of typical Char syndrome.


Assuntos
Permeabilidade do Canal Arterial , Humanos , Permeabilidade do Canal Arterial/genética , Fator de Transcrição AP-2/genética , Anormalidades Múltiplas/genética , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Crista Neural/metabolismo , Crista Neural/embriologia , Face/anormalidades , Dedos/anormalidades
17.
J Oral Biosci ; 66(2): 339-348, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750954

RESUMO

OBJECTIVES: The development of bio-three-dimensional (bio-3D) printers has led to significant advances in regenerative medicine. Three-dimensional constructs, including spheroids, are maintained by extracellular matrix proteins secreted by cells so that the cells can be cultured in conditions closer to the physiological environment. This study aimed to create a useful 3D construct as a model of the dentin-pulp complex. METHODS: We examined the expression patterns of extracellular matrix proteins and cell proliferation areas in a 3D construct created using O9-1 cells derived from cranial neural crest cells of mice. The 3D construct was created by sticking the spheroid cultures onto a needle array using a bio-3D printer. RESULTS: Cell proliferation areas along with characteristic expression of tenascin C and DMP1 were evaluated. The expression of tenascin C and DMP1 was significantly enhanced in the spheroids compared to that in two-dimensional cultures. Moreover, cell proliferation regions and tenascin C expression were confirmed in the outer layer of spheroids in the embryonic stem cell medium, with insignificant DMP1 expression being observed. Interestingly, in a 3D construct cultured in calcification-induction medium, DMP1 expression was promoted, and DMP1-positive cells existed in the outermost layer without overlapping with tenascin C expression. CONCLUSIONS: The extracellular matrix proteins, tenascin C and DMP1, were expressed in a polarized manner in spheroids and 3D constructs, similar to the findings in the dental papilla. Therefore, these 3D constructs show potential as artificial models for studying odontogenesis.


Assuntos
Proliferação de Células , Proteínas da Matriz Extracelular , Crista Neural , Impressão Tridimensional , Tenascina , Crista Neural/citologia , Crista Neural/metabolismo , Animais , Camundongos , Tenascina/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Linhagem Celular , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Engenharia Tecidual/métodos
18.
Curr Top Dev Biol ; 159: 132-167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38729675

RESUMO

The primary senses-touch, taste, sight, smell, and hearing-connect animals with their environments and with one another. Aside from the eyes, the primary sense organs of vertebrates and the peripheral sensory pathways that relay their inputs arise from two transient stem cell populations: the neural crest and the cranial placodes. In this chapter we consider the senses from historical and cultural perspectives, and discuss the senses as biological faculties. We begin with the embryonic origin of the neural crest and cranial placodes from within the neural plate border of the ectodermal germ layer. Then, we describe the major chemical (i.e. olfactory and gustatory) and mechanical (i.e. vestibulo-auditory and somatosensory) senses, with an emphasis on the developmental interactions between neural crest and cranial placodes that shape their structures and functions.


Assuntos
Crista Neural , Animais , Crista Neural/citologia , Crista Neural/embriologia , Crista Neural/fisiologia , Humanos , Sensação/fisiologia , Órgãos dos Sentidos/embriologia , Órgãos dos Sentidos/fisiologia , Órgãos dos Sentidos/citologia , Vertebrados/embriologia , Vertebrados/fisiologia
19.
J Cutan Pathol ; 51(8): 594-597, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38698729

RESUMO

A neurofibroma with focal glomus-like body differentiation is an unusual phenomenon recently encountered in an excision specimen from the right lateral distal forearm of a 26-year-old man. Glomus cells are modified smooth muscle cells normally present in glomus-like bodies but can also be found in glomus tumors (GT) or lesions considered in the spectrum of GT, including myopericytoma, myofibroma, and angiolipoma. Neurofibromas are peripheral nerve sheath tumors derived from the neural crest cells. While both GT and its variants and neurofibroma are thought to be derived from different cell types, there is growing evidence that glomus cells have a neural crest origin. This is based on multiple theories, with some overlapping pathways, including neural crest cell differentiation, Schwann cell reprogramming, VEGF expression, and NF1 gene biallelic inactivation. This report adds to the growing evidence of possible neural crest origin for glomus cells and would help explain finding glomus-like bodies scattered through a neurofibroma.


Assuntos
Tumor Glômico , Neurofibroma , Humanos , Masculino , Adulto , Tumor Glômico/patologia , Tumor Glômico/metabolismo , Tumor Glômico/genética , Neurofibroma/patologia , Neurofibroma/metabolismo , Crista Neural/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Células de Schwann/patologia , Células de Schwann/metabolismo , Antebraço/patologia
20.
Differentiation ; 138: 100782, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38810379

RESUMO

The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant talpid2 (ta2) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel's cartilage. We found an ectopic epithelial BMP signaling domain in the ta2 mandibular prominence (MNP) that correlated with the subsequent expansion of SOX9+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.


Assuntos
Mandíbula , Crista Neural , Animais , Crista Neural/citologia , Crista Neural/metabolismo , Camundongos , Mandíbula/crescimento & desenvolvimento , Mandíbula/metabolismo , Padronização Corporal/genética , Cartilagem/metabolismo , Cartilagem/crescimento & desenvolvimento , Cartilagem/citologia , Cílios/metabolismo , Cílios/genética , Mesoderma/citologia , Mesoderma/metabolismo , Mesoderma/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Transdução de Sinais , Diferenciação Celular , Embrião de Galinha , Galinhas/genética , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOX9/genética
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