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1.
Am J Hum Genet ; 111(10): 2232-2252, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39226899

RESUMEN

The BAF chromatin remodeler regulates lineage commitment including cranial neural crest cell (CNCC) specification. Variants in BAF subunits cause Coffin-Siris syndrome (CSS), a congenital disorder characterized by coarse craniofacial features and intellectual disability. Approximately 50% of individuals with CSS harbor variants in one of the mutually exclusive BAF subunits, ARID1A/ARID1B. While Arid1a deletion in mouse neural crest causes severe craniofacial phenotypes, little is known about the role of ARID1A in CNCC specification. Using CSS-patient-derived ARID1A+/- induced pluripotent stem cells to model CNCC specification, we discovered that ARID1A-haploinsufficiency impairs epithelial-to-mesenchymal transition (EMT), a process necessary for CNCC delamination and migration from the neural tube. Furthermore, wild-type ARID1A-BAF regulates enhancers associated with EMT genes. ARID1A-BAF binding at these enhancers is impaired in heterozygotes while binding at promoters is unaffected. At the sequence level, these EMT enhancers contain binding motifs for ZIC2, and ZIC2 binding at these sites is ARID1A-dependent. When excluded from EMT enhancers, ZIC2 relocates to neuronal enhancers, triggering aberrant neuronal gene activation. In mice, deletion of Zic2 impairs NCC delamination, while ZIC2 overexpression in chick embryos at post-migratory neural crest stages elicits ectopic delamination from the neural tube. These findings reveal an essential ARID1A-ZIC2 axis essential for EMT and CNCC delamination.


Asunto(s)
Proteínas de Unión al ADN , Transición Epitelial-Mesenquimal , Cara , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Cuello , Cresta Neural , Factores de Transcripción , Cresta Neural/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transición Epitelial-Mesenquimal/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Humanos , Discapacidad Intelectual/genética , Micrognatismo/genética , Animales , Cara/anomalías , Cara/embriología , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/patología , Cuello/anomalías , Cuello/embriología , Ratones , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Haploinsuficiencia , Elementos de Facilitación Genéticos/genética , Deformidades Congénitas del Pie/genética , Deformidades Congénitas del Pie/patología , Regulación del Desarrollo de la Expresión Génica , Anomalías Múltiples
2.
Am J Hum Genet ; 110(5): 846-862, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37086723

RESUMEN

Craniosynostosis (CS) is the most common congenital cranial anomaly. Several Mendelian forms of syndromic CS are well described, but a genetic etiology remains elusive in a substantial fraction of probands. Analysis of exome sequence data from 526 proband-parent trios with syndromic CS identified a marked excess (observed 98, expected 33, p = 4.83 × 10-20) of damaging de novo variants (DNVs) in genes highly intolerant to loss-of-function variation (probability of LoF intolerance > 0.9). 30 probands harbored damaging DNVs in 21 genes that were not previously implicated in CS but are involved in chromatin modification and remodeling (4.7-fold enrichment, p = 1.1 × 10-11). 17 genes had multiple damaging DNVs, and 13 genes (CDK13, NFIX, ADNP, KMT5B, SON, ARID1B, CASK, CHD7, MED13L, PSMD12, POLR2A, CHD3, and SETBP1) surpassed thresholds for genome-wide significance. A recurrent gain-of-function DNV in the retinoic acid receptor alpha (RARA; c.865G>A [p.Gly289Arg]) was identified in two probands with similar CS phenotypes. CS risk genes overlap with those identified for autism and other neurodevelopmental disorders, are highly expressed in cranial neural crest cells, and converge in networks that regulate chromatin modification, gene transcription, and osteoblast differentiation. Our results identify several CS loci and have major implications for genetic testing and counseling.


Asunto(s)
Craneosinostosis , Tretinoina , Humanos , Mutación , Craneosinostosis/genética , Regulación de la Expresión Génica , Cromatina , Predisposición Genética a la Enfermedad
3.
Development ; 150(19)2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37812056

RESUMEN

The evolution of a unique craniofacial complex in vertebrates made possible new ways of breathing, eating, communicating and sensing the environment. The head and face develop through interactions of all three germ layers, the endoderm, ectoderm and mesoderm, as well as the so-called fourth germ layer, the cranial neural crest. Over a century of experimental embryology and genetics have revealed an incredible diversity of cell types derived from each germ layer, signaling pathways and genes that coordinate craniofacial development, and how changes to these underlie human disease and vertebrate evolution. Yet for many diseases and congenital anomalies, we have an incomplete picture of the causative genomic changes, in particular how alterations to the non-coding genome might affect craniofacial gene expression. Emerging genomics and single-cell technologies provide an opportunity to obtain a more holistic view of the genes and gene regulatory elements orchestrating craniofacial development across vertebrates. These single-cell studies generate novel hypotheses that can be experimentally validated in vivo. In this Review, we highlight recent advances in single-cell studies of diverse craniofacial structures, as well as potential pitfalls and the need for extensive in vivo validation. We discuss how these studies inform the developmental sources and regulation of head structures, bringing new insights into the etiology of structural birth anomalies that affect the vertebrate head.


Asunto(s)
Evolución Biológica , Cráneo , Animales , Humanos , Vertebrados , Cresta Neural/metabolismo , Biología Evolutiva , Regulación del Desarrollo de la Expresión Génica
4.
Semin Cell Dev Biol ; 138: 45-53, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-35331627

RESUMEN

Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout the embryo, consistent with its ectodermal origin, cranial neural crest-derived cells (CNCCs) generate many connective tissue and skeletal cell types in common with mesoderm. Whether this ectoderm-derived mesenchyme (ectomesenchyme) potential reflects a distinct developmental origin from other CNCC lineages, and/or epigenetic reprogramming of the ectoderm, remains debated. Whereas decades of lineage tracing studies have defined the potential of CNCC ectomesenchyme, these are being revisited by modern genetic techniques. Recent work is also shedding light on the extent to which intrinsic and extrinsic cues determine ectomesenchyme potential, and whether maintenance or reacquisition of CNCC multipotency influences craniofacial repair.


Asunto(s)
Mesodermo , Cresta Neural , Cresta Neural/metabolismo , Ectodermo/metabolismo , Embrión de Mamíferos
5.
Development ; 149(23)2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36367707

RESUMEN

Certain cranial neural crest cells are uniquely endowed with the ability to make skeletal cell types otherwise only derived from mesoderm. As these cells migrate into the pharyngeal arches, they downregulate neural crest specifier genes and upregulate so-called ectomesenchyme genes that are characteristic of skeletal progenitors. Although both external and intrinsic factors have been proposed as triggers of this transition, the details remain obscure. Here, we report the Nr2f nuclear receptors as intrinsic activators of the ectomesenchyme program: zebrafish nr2f5 single and nr2f2;nr2f5 double mutants show marked delays in upregulation of ectomesenchyme genes, such as dlx2a, prrx1a, prrx1b, sox9a, twist1a and fli1a, and in downregulation of sox10, which is normally restricted to early neural crest and non-ectomesenchyme lineages. Mutation of sox10 fully rescued skeletal development in nr2f5 single but not nr2f2;nr2f5 double mutants, but the initial ectomesenchyme delay persisted in both. Sox10 perdurance thus antagonizes the recovery but does not explain the impaired ectomesenchyme transition. Unraveling the mechanisms of Nr2f function will help solve the enduring puzzle of how cranial neural crest cells transition to the skeletal progenitor state.


Asunto(s)
Placa Neural , Pez Cebra , Animales , Pez Cebra/genética , Cresta Neural , Mesodermo , Receptores Citoplasmáticos y Nucleares/genética , Regulación del Desarrollo de la Expresión Génica
6.
Development ; 149(18)2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-36125128

RESUMEN

Hippo signaling, an evolutionarily conserved kinase cascade involved in organ size control, plays key roles in various tissue developmental processes, but its role in craniofacial development remains poorly understood. Using the transgenic Wnt1-Cre2 driver, we inactivated the Hippo signaling components Lats1 and Lats2 in the cranial neuroepithelium of mouse embryos and found that the double conditional knockout (DCKO) of Lats1/2 resulted in neural tube and craniofacial defects. Lats1/2 DCKO mutant embryos had microcephaly with delayed and defective neural tube closure. Furthermore, neuroepithelial cell shape and architecture were disrupted within the cranial neural tube in Lats1/2 DCKO mutants. RNA sequencing of embryonic neural tubes revealed increased TGFB signaling in Lats1/2 DCKO mutants. Moreover, markers of epithelial-to-mesenchymal transition (EMT) were upregulated in the cranial neural tube. Inactivation of Hippo signaling downstream effectors, Yap and Taz, suppressed neuroepithelial defects, aberrant EMT and TGFB upregulation in Lats1/2 DCKO embryos, indicating that LATS1/2 function via YAP and TAZ. Our findings reveal important roles for Hippo signaling in modulating TGFB signaling during neural crest EMT.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Transición Epitelial-Mesenquimal/genética , Ratones , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/genética , Cráneo , Factor de Crecimiento Transformador beta/metabolismo
7.
Dev Dyn ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320016

RESUMEN

BACKGROUND: Embryonic craniofacial development involves several cellular and molecular events that are evolutionarily conserved among vertebrates. Vertebrate models such as mice and zebrafish have been used to investigate the molecular and cellular etiologies underlying human craniofacial disorders, including orofacial clefts. However, the molecular mechanisms underlying embryonic development in these two species are unknown. Therefore, elucidating the shared mechanisms of craniofacial development between disease models is crucial to understanding the underlying mechanisms of phenotypes in individual species. RESULTS: We selected mice and zebrafish as model organisms to compare various events during embryonic craniofacial development. We identified genes (Sox9, Zfhx3 and 4, Cjun, and Six1) exhibiting similar temporal expression patterns between these species through comprehensive and stage-matched gene expression analyses. Expression analysis revealed similar gene expression in hypothetically corresponding tissues, such as the mice palate and zebrafish ethmoid plate. Furthermore, loss-of-function analysis of Zfhx4/zfhx4, a causative gene of human craniofacial anomalies including orofacial cleft, in both species resulted in deformed skeletal elements such as the palatine and ethmoid plate in mice and zebrafish, respectively. CONCLUSIONS: These results demonstrate that these disease models share common molecular mechanisms, highlighting their usefulness in modeling craniofacial defects in humans.

8.
Development ; 148(13)2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34128978

RESUMEN

Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One crucial role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. As seen in Ift20 mutant mice, disruption of neural crest-specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared with either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.


Asunto(s)
Proteínas de la Matriz de Golgi/metabolismo , Cráneo/crecimiento & desarrollo , Cráneo/metabolismo , Animales , Calcificación Fisiológica , Proteínas Portadoras/metabolismo , Diferenciación Celular , Proliferación Celular , Colágeno/metabolismo , Proteínas del Citoesqueleto/metabolismo , Aparato de Golgi/genética , Aparato de Golgi/metabolismo , Proteínas de la Matriz de Golgi/genética , Ratones , Ratones Noqueados , Cresta Neural/metabolismo , Osteoblastos , Osteogénesis , Proteómica
9.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38255806

RESUMEN

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.


Asunto(s)
Microtia Congénita , Imidas , Quinolinas , Pez Cebra , Animales , Apoptosis/genética , beta Catenina/genética , Pez Cebra/genética
10.
J Proteome Res ; 22(10): 3264-3274, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37616547

RESUMEN

The epithelial-to-mesenchymal transition (EMT) and migration of cranial neural crest cells within the midbrain are critical processes that permit proper craniofacial patterning in the early embryo. Disruptions in these processes not only impair development but also lead to various diseases, underscoring the need for their detailed understanding at the molecular level. The chick embryo has served historically as an excellent model for human embryonic development, including cranial neural crest cell EMT and migration. While these developmental events have been characterized transcriptionally, studies at the protein level have not been undertaken to date. Here, we applied mass spectrometry (MS)-based proteomics to establish a deep proteomics profile of the chick midbrain region during early embryonic development. Our proteomics method combines optimal lysis conditions, offline fractionation, separation on a nanopatterned stationary phase (µPAC) using nanoflow liquid chromatography, and detection using quadrupole-ion trap-Orbitrap tribrid high-resolution tandem MS. Identification of >5900 proteins and >450 phosphoproteins in this study marks the deepest coverage of the chick midbrain proteome to date. These proteins have known roles in pathways related to neural crest cell EMT and migration such as signaling, proteolysis/extracellular matrix remodeling, and transcriptional regulation. This study offers valuable insight into important developmental processes occurring in the midbrain region and demonstrates the utility of proteomics for characterization of tissue microenvironments during chick embryogenesis.

11.
Cell Mol Life Sci ; 79(3): 158, 2022 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-35220463

RESUMEN

Calvarial bone is one of the most complex sequences of developmental events in embryology, featuring a uniquely transient, pluripotent stem cell-like population known as the cranial neural crest (CNC). The skull is formed through intramembranous ossification with distinct tissue lineages (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Due to CNC's vast cell fate potential, in response to a series of inductive secreted cues including BMP/TGF-ß, Wnt, FGF, Notch, Hedgehog, Hippo and PDGF signaling, CNC enables generations of a diverse spectrum of differentiated cell types in vivo such as osteoblasts and chondrocytes at the craniofacial level. In recent years, since the studies from a genetic mouse model and single-cell sequencing, new discoveries are uncovered upon CNC patterning, differentiation, and the contribution to the development of cranial bones. In this review, we summarized the differences upon the potential gene regulatory network to regulate CNC derived osteogenic potential in mouse and human, and highlighted specific functions of genetic molecules from multiple signaling pathways and the crosstalk, transcription factors and epigenetic factors in orchestrating CNC commitment and differentiation into osteogenic mesenchyme and bone formation. Disorders in gene regulatory network in CNC patterning indicate highly close relevance to clinical birth defects and diseases, providing valuable transgenic mouse models for subsequent discoveries in delineating the underlying molecular mechanisms. We also emphasized the potential regenerative alternative through scientific discoveries from CNC patterning and genetic molecules in interfering with or alleviating clinical disorders or diseases, which will be beneficial for the molecular targets to be integrated for novel therapeutic strategies in the clinic.


Asunto(s)
Diferenciación Celular , Redes Reguladoras de Genes/genética , Osteogénesis , Animales , Proteínas Morfogenéticas Óseas/metabolismo , Mesodermo/citología , Mesodermo/metabolismo , Cresta Neural/citología , Cresta Neural/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
12.
Oral Dis ; 29(6): 2449-2462, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36648381

RESUMEN

The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis.


Asunto(s)
Síndrome de Goldenhar , Humanos , Síndrome de Goldenhar/cirugía , Síndrome de Goldenhar/complicaciones , Asimetría Facial/etiología , Mandíbula/patología
13.
Int J Mol Sci ; 24(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37895082

RESUMEN

Bone growth plate abnormalities and skull shape defects are seen in hypophosphatasia, a heritable disorder in humans that occurs due to the deficiency of tissue nonspecific alkaline phosphatase (TNAP, Alpl) enzyme activity. The abnormal development of the cranial base growth plates (synchondroses) and abnormal skull shapes have also been demonstrated in global Alpl-/- mice. To distinguish local vs. systemic effects of TNAP on skull development, we utilized P0-Cre to knockout Alpl only in cranial neural crest-derived tissues using Alpl flox mice. Here, we show that Alpl deficiency using P0-Cre in cranial neural crest leads to skull shape defects and the deficient growth of the intersphenoid synchondrosis (ISS). ISS chondrocyte abnormalities included increased proliferation in resting and proliferative zones with decreased apoptosis in hypertrophic zones. ColX expression was increased, which is indicative of premature differentiation in the absence of Alpl. Sox9 expression was increased in both the resting and prehypertrophic zones of mutant mice. The expression of Parathyroid hormone related protein (PTHrP) and Indian hedgehog homolog (IHH) were also increased. Finally, cranial base organ culture revealed that inorganic phosphate (Pi) and pyrophosphate (PPi) have specific effects on cell signaling and phenotype changes in the ISS. Together, these results demonstrate that the TNAP expression downstream of Alpl in growth plate chondrocytes is essential for normal development, and that the mechanism likely involves Sox9, PTHrP, IHH and PPi.


Asunto(s)
Fosfatasa Alcalina , Condrocitos , Animales , Ratones , Fosfatasa Alcalina/metabolismo , Diferenciación Celular , Condrocitos/metabolismo , Cresta Neural/metabolismo , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Base del Cráneo/metabolismo
14.
Dev Dyn ; 251(8): 1250-1266, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35338756

RESUMEN

The classical anatomist Drew Noden spearheaded craniofacial research, laying the foundation for our modern molecular understanding of development, evolution, and disorders of the craniofacial skeleton. His work revealed the origin of cephalic musculature and the role of cranial neural crest (CNC) in early formation and patterning of the head musculoskeletal structures. Much of modern cranial tendon research advances a foundation of knowledge that Noden built using classical quail-chick transplantation experiments. This elegant avian chimeric system involves grafting of donor quail cells into host chick embryos to identify the cell types they can form and their interactions with the surrounding tissues. In this review, we will give a brief background of vertebrate head formation and the impact of CNC on the patterning, development, and evolution of the head musculoskeletal attachments. Using the zebrafish as a model system, we will discuss examples of modifications of craniofacial structures in evolution with a special focus on the role of tendon and ligaments. Lastly, we will discuss pathologies in craniofacial tendons and the importance of understanding the molecular and cellular dynamics during craniofacial tendon development in human disease.


Asunto(s)
Cresta Neural , Pez Cebra , Animales , Embrión de Pollo , Humanos , Codorniz , Cráneo , Tendones
15.
Dev Dyn ; 251(7): 1209-1222, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35147267

RESUMEN

BACKGROUND: Absence of Golgi microtubule-associated protein 210 (GMAP210), encoded by the TRIP11 gene, results in achondrogenesis. Although TRIP11 is thought to be specifically required for chondrogenesis, human fetuses with the mutation of TRIP11 also display bony skull defects where chondrocytes are usually not present. This raises an important question of how TRIP11 functions in bony skull development. RESULTS: We disrupted Trip11 in neural crest-derived cell populations, which are critical for developing skull in mice. In Trip11 mutant skulls, expression levels of ER stress markers were increased compared to controls. Morphological analysis of electron microscopy data revealed swollen ER in Trip11 mutant skulls. Unexpectedly, we also found that Golgi stress increased in Trip11 mutant skulls, suggesting that both ER and Golgi stress-induced cell death may lead to osteopenia-like phenotypes in Trip11 mutant skulls. These data suggest that Trip11 plays pivotal roles in the regulation of ER and Golgi stress, which are critical for osteogenic cell survival. CONCLUSION: We have recently reported that the molecular complex of ciliary protein and GMAP210 is required for collagen trafficking. In this paper, we further characterized the important role of Trip11 being possibly involved in the regulation of ER and Golgi stress during skull development.


Asunto(s)
Proteínas del Citoesqueleto , Estrés del Retículo Endoplásmico , Aparato de Golgi , Cresta Neural , Osteocondrodisplasias , Animales , Proteínas del Citoesqueleto/genética , Aparato de Golgi/metabolismo , Humanos , Ratones , Osteocondrodisplasias/metabolismo , Cráneo , Factores de Transcripción/metabolismo
16.
Dev Biol ; 471: 97-105, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33340512

RESUMEN

During neurulation, cranial neural crest cells (CNCCs) migrate long distances from the neural tube to their terminal site of differentiation. The pathway traveled by the CNCCs defines the blueprint for craniofacial construction, abnormalities of which contribute to three-quarters of human birth defects. Biophysical cues like naturally occurring electric fields (EFs) have been proposed to be one of the guiding mechanisms for CNCC migration from the neural tube to identified position in the branchial arches. Such endogenous EFs can be mimicked by applied EFs of physiological strength that has been reported to guide the migration of amphibian and avian neural crest cells (NCCs), namely galvanotaxis or electrotaxis. However, the behavior of mammalian NCCs in external EFs has not been reported. We show here that mammalian CNCCs migrate towards the anode in direct current (dc) EFs. Reversal of the field polarity reverses the directedness. The response threshold was below 30 â€‹mV/mm and the migration directedness and displacement speed increased with increase in field strength. Both CNCC line (O9-1) and primary mouse CNCCs show similar galvanotaxis behavior. Our results demonstrate for the first time that the mammalian CNCCs respond to physiological EFs by robust directional migration towards the anode in a voltage-dependent manner.


Asunto(s)
Región Branquial/embriología , Diferenciación Celular , Movimiento Celular , Electricidad , Transducción de Señal , Animales , Región Branquial/citología , Línea Celular , Ratones , Cresta Neural/citología
17.
Yi Chuan ; 44(12): 1089-1102, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36927555

RESUMEN

The craniofacial features endow vertebrates with unparalleled evolutionary advantages. The craniofacial is composed of bone, cartilage, nerves, and connective tissues mainly developed from cranial neural crest cells (cNCCs). These tissues form complex organs which enable vertebrates to have powerful neural and sensory systems. NCCs are groups of migratory and pluripotent cells that are specific to vertebrates. The specification, premigration and migration, proliferation, and fate determination of the NCCs are precisely and sequentially controlled by gene regulatory networks, to ensure the ordered and accurate development of the craniofacial region. The craniofacial region represents a combined set of highly heritable phenotypes, which could be illustrated by the inherited facial features between relatives but perceptible differences among non-relatives. Such phenomena are termed heredity and variation, which are in accordance with the precision and plasticity of cNCCs gene regulatory network, respectively. Evidence has shown that genetic variations within the regulatory network alter the proliferation and differentiation of NCCs within a tolerable range, while deleterious mutations will lead to craniofacial malformations. In this review, we first summarize the development procedure of NCCs and their gene regulatory networks and then provide an overview on the genetic basis of the facial morphology and malformations. This review will benefit the understanding of craniofacial development and the prevention of craniofacial diseases.


Asunto(s)
Cresta Neural , Vertebrados , Animales , Cresta Neural/fisiología , Diferenciación Celular , Redes Reguladoras de Genes
18.
Semin Cell Dev Biol ; 91: 13-22, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-29248471

RESUMEN

The skull is a vertebrate novelty. Morphological adaptations of the skull are associated with major evolutionary transitions, including the shift to a predatory lifestyle and the ability to masticate while breathing. These adaptations include the chondrocranium, dermatocranium, articulated jaws, primary and secondary palates, internal choanae, the middle ear, and temporomandibular joint. The incredible adaptive diversity of the vertebrate skull indicates an underlying bauplan that promotes evolvability. Comparative studies in craniofacial development suggest that the craniofacial bauplan includes three secondary organizers, two that are bilaterally placed at the Hinge of the developing jaw, and one situated in the midline of the developing face (the FEZ). These organizers regulate tissue interactions between the cranial neural crest, the neuroepithelium, and facial and pharyngeal epithelia that regulate the development and evolvability of the craniofacial skeleton.


Asunto(s)
Evolución Biológica , Huesos Faciales/embriología , Cresta Neural/embriología , Cráneo/embriología , Animales , Tipificación del Cuerpo/genética , Huesos Faciales/anatomía & histología , Huesos Faciales/metabolismo , Peces/anatomía & histología , Peces/embriología , Peces/genética , Regulación del Desarrollo de la Expresión Génica , Cresta Neural/anatomía & histología , Cresta Neural/metabolismo , Cráneo/anatomía & histología , Cráneo/metabolismo
19.
Semin Cell Dev Biol ; 91: 45-54, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-29784581

RESUMEN

The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-Beta, Wnt and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell populations that are required to form the tongue. In humans, a number of congenital abnormalities that affect gross morphology of the tongue have also been described, occurring in isolation or as part of a developmental syndrome, which can greatly impact on the health and well-being of affected individuals. These anomalies can range from an absence of tongue formation (aglossia) through to diminutive (microglossia), enlarged (macroglossia) or bifid tongue. Here, we present an overview of the gross anatomy and embryology of mammalian tongue development, focusing on the molecular processes underlying formation of the musculature and connective tissues within this organ. We also survey the clinical presentation of tongue anomalies seen in human populations, whilst considering their developmental and genetic etiology.


Asunto(s)
Tejido Conectivo/embriología , Músculos/embriología , Cresta Neural/embriología , Lengua/embriología , Animales , Tejido Conectivo/anatomía & histología , Tejido Conectivo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Mamíferos/anatomía & histología , Mamíferos/embriología , Mamíferos/genética , Músculos/citología , Músculos/metabolismo , Cresta Neural/citología , Cresta Neural/metabolismo , Organogénesis/genética , Transducción de Señal/genética , Lengua/citología , Lengua/metabolismo
20.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525669

RESUMEN

Maxillofacial hard tissues have several differences compared to bones of other localizations of the human body. These could be due to the different embryological development of the jaw bones compared to the extracranial skeleton. In particular, the immigration of neuroectodermally differentiated cells of the cranial neural crest (CNC) plays an important role. These cells differ from the mesenchymal structures of the extracranial skeleton. In the ontogenesis of the jaw bones, the development via the intermediate stage of the pharyngeal arches is another special developmental feature. The aim of this review was to illustrate how the development of maxillofacial hard tissues occurs via the cranial neural crest and pharyngeal arches, and what significance this could have for relevant pathologies in maxillofacial surgery, dentistry and orthodontic therapy. The pathogenesis of various growth anomalies and certain syndromes will also be discussed.


Asunto(s)
Región Branquial/fisiología , Huesos Faciales/crecimiento & desarrollo , Cresta Neural/fisiología , Diferenciación Celular , Movimiento Celular , Regulación del Desarrollo de la Expresión Génica , Humanos , Desarrollo Maxilofacial , Transducción de Señal
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