RESUMO
Neural crest cells (NCCs) are a multipotent and transient cell population that gives rise to many important tissues during human embryogenesis. Disturbances that occur during NCCs development may lead to numerous types of diseases and syndromes, which are called neurocristopathies. NCCs in vitro modeling enables the access to cellular, genetic, and biochemical information about the neural crest development and its derivatives. By using cells derived from patients with neurocristopathies it is possible to study the cellular and genetic mechanisms behind each disease in a specific and trustworthy manner, as well as to contribute to the development of prospective treatments. Here, we describe a protocol of 19 days, capable of efficiently generating NCCs from human induced pluripotent stem cells (hiPSCs). This differentiation process recapitulates the intermediate stage of neural plate border-like cells (NBCs), the epithelial to mesenchymal transition (EMT), and enables further generation of NCCs derivatives, such as Schwann cells, smooth muscle cells, melanocytes, peripheral neurons, adipocytes, osteoblasts, and chondrocytes.
Assuntos
Células-Tronco Pluripotentes Induzidas , Crista Neural , Diferenciação Celular , Transição Epitelial-Mesenquimal , Humanos , Placa Neural , Estudos ProspectivosRESUMO
Las cardiopatías congénitas corresponden al grupo de anomalías del desarrollo que se presentan con mayor frecuencia. Durante el desarrollo cardíaco participan distintos linajes celulares, donde destacan las Células de la Cresta Neural (CCN) por su amplia gama de derivados embriológicos y la susceptibilidad de afectar a múltiples sistemas si su función es alterada. El objetivo fue determinar el rol que cumplen las CCN durante el desarrollo cardíaco y las cardiopatías congénitas asociadas. Se diseñó un estudio descriptivo en base a una revisión sistemática de la literatura de las bases de datos MEDLINE y Scopus, utilizando la combinación de términos MeSH: ("Heart Diseases/congenital" OR "Heart Diseases/embriology" OR "Heart Diseases/etiology" OR "Heart Disesaes/epidemiology") AND ("Neural Crest/abnormalities"). Se restringió la búsqueda a artículos de los últimos 10 años. De un total de 35 artículos obtenidos, 22 fueron incluidos para su revisión por estar relacionados con los objetivos de este estudio, excluyéndose duplicados entre bases de datos. Posteriormente se hizo un análisis individual y en conjunto de la información obtenida de los artículos seleccionados. La evidencia indica la participación directa o indirecta de las CCN durante la formación de las estructuras derivadas del polo arterioso del corazón en desarrollo, los grandes vasos arteriales y sus ramas colaterales, así como en su inervación y sistema de conducción. La alteración del funcionamiento normal de las CCN produce fenotipos cardíacos alterados, siendo la persistencia del tronco arterioso, doble salida ventricular derecha, defectos septales interventriculares y malformación de los aparatos valvares aórtico y pulmonar, los más frecuentes.
Congenital heart defects are the group of most frequent anomalies of development. Cardiac development in different cell lines, which include the Neural crest cells (NCC) for their wide range of embryological derivatives and susceptibility to affect multiple systems if their function is altered participate. The objective was to determine the role of the NCC during heart development and associated congenital heart disease. A descriptive study was designed based on a systematic review of the literature from the MEDLINE and Scopus data, using a combination of MeSH terms ("Heart Diseases / congenital" OR "Heart Diseases / Embryology" OR "Heart Diseases/etiology "OR" Heart Diseases/epidemiology ") AND ("Neural Crest/abnormalities"). Search for articles in the last 10 years was restricted. From a total of 35 articles retrieved, 22 were included related to the objectives of this study for review, excluding duplicated between databases. Subsequently, an individual and joint analysis was realized with the information from the selected items. Evidence indicates the direct or indirect involvement of NCC during the formation of the structures derived from arterial pole of the developing heart, the large arterial vessels and their collateral branches, as well as its innervation and conduction system. The disruption of normal operation of the NCC produces altered cardiac phenotypes, with the Persistence Truncus Arteriosus, Double-Outlet Right Ventricle, ventricular Septal Defects and malformation of the most common valvular aortic and pulmonary devices.
Assuntos
Humanos , Cardiopatias Congênitas/embriologia , Crista Neural/anormalidades , Cardiopatias Congênitas/etiologiaRESUMO
Cell differentiation is essential for maxillaries and tooth development. Facial mesenchymal tissue is formed by neural crest cells (NC). These cells are highly migratory, giving rise to various cell types, considered with a high level of plasticity, indicating that they contain progenitor cells with a great power of differentiation. In this study, it was analyzed the presence of NC cell progenitors and mesenchymal stem cells (MSC) during maxillaries osteogenesis and odontogenesis in rats. Histological slides were collected in two phases: embryonic age of 15 and 17 days; 2, 4 and 7 days after birth. Immunohistochemistry for MSC markers (Osterix) and NC cells (Sox10, HNK1) was performed. The results showed positive expression for Osterix and HNK1 in undifferentiated ectomesenchymal cells in early and late stages; Sox10 was present only in early stages in undifferentiated cells. All markers were present in differentiated cells. Although the experiments performed do not allow us to explain a possible role for Osx, HNK1 and Sox10 in both differentiated and undifferentiated cells during osteogenesis and odontogenesis, it had shown important results not yet described: the presence of HNK1 and Sox10 in osteoblasts and odontoblasts in late development stages and in the tooth germ epithelial cells and ameloblasts.
Assuntos
Células-Tronco Embrionárias/citologia , Crista Neural/citologia , Odontogênese/fisiologia , Osteogênese/fisiologia , Fatores de Transcrição SOXE/metabolismo , Sulfotransferases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/metabolismo , Odontoblastos/citologia , Odontoblastos/metabolismo , Ratos Wistar , Germe de Dente/citologiaRESUMO
Chemotactic cell migration is triggered by extracellular concentration gradients of molecules segregated by target fields. Neural crest cells (NCCs), paradigmatic as an accurately moving cell population, undergo wide dispersion along multiple pathways, invading with precision defined sites of the embryo to differentiate into many derivatives. This report addresses the involvement of NT-3 in early colonization by cephalic NCCs invading the optic vesicle region. The results of in vitro and in vivo approaches showed that NCCs migrate directionally up an NT-3 concentration gradient. We also demonstrated the expression of NT-3 in the ocular region as well as their functional TrkB, TrkC and p75 receptors on cephalic NCCs. On whole-mount embryo, a perturbed distribution of NCCs colonizing the optic vesicle target field was shown after morpholino cancelation of cephalic NT-3 or TrkC receptor on NCCs, as well as in situ blocking of TrkC receptor of mesencephalic NCCs by specific antibody released from inserted microbeads. The present results strongly suggest that, among other complementary cell guidance factor(s), the chemotactic response of NCCs toward the ocular region NT-3 gradient is essential for spatiotemporal cell orientation, amplifying the functional scope of this neurotrophic factor as a molecular guide for the embryo cells, besides its well-known canonical functions.
Assuntos
Quimiotaxia , Mesencéfalo/citologia , Crista Neural/citologia , Neurotrofina 3/metabolismo , Animais , Proliferação de Células , Embrião de Galinha , Galinhas , Crista Neural/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de SinaisRESUMO
El desarrollo embrionario de las regiones facial, del cuello, cavidades nasales y oral en conjunto con las glándulas asociadas, involucra el crecimiento y fusión tridimensional de múltiples procesos. Existe participación de elementos derivados de las 3 capas embrionarias locales y adicionalmente de células derivas de la cresta neural, procedentes de los rombómeros vecinos. Estas últimas se ven involucradas en la formación del esqueleto local, entre otras estructuras. El estudio evolutivo desde los vertebrados sin mandíbula nos enseña como se expresan los genes Hox en las diferentes especies, y como esto determina la formación de diferentes estructuras. En la siguiente revisión contemplamos algunos aspectos morfológicos, moleculares y evolutivos básicos del desarrollo facial y cervical, con énfasis en mamíferos con un epílogo referente a las malformaciones de la región en humanos.
The embryonic development of the facial area, neck, nasal, oral and pharyngeal cavities with glands, involves growth and fusion of multi-dimensional processes. There is involvement of elements from the embryo-derived local 3 layers cells further neural crest derived cells from the neighbors rhombomeres. The neural crest cells are involved in the formation of local skeleton, among other structures. The study of evolution from jawless vertebrates shows us how Hox genes are expressed in different species, and how this determines the formation of different structures. The following review contemplate some morphological, molecular and evolutionary basis of facial and neck development, with emphasis on mammals with an epilogue concerning to the face and neck malformations in humans.