The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development / 国际口腔科学杂志·英文版

The cranial neural crest plays a fundamental role in orofacial development and morphogenesis. Accordingly, mutations with impact on the cranial neural crest and its development lead to orofacial malformations such as cleft lip and palate. As a pluripotent and dynamic cell population, the cranial neural crest undergoes vast transcriptional and epigenomic alterations throughout the formation of facial structures pointing to an essential role of factors regulating chromatin state or transcription levels. Using CRISPR/Cas9-guided genome editing and conditional mutagenesis in the mouse, we here show that inactivation of Kat5 or Ep400 as the two essential enzymatic subunits of the Tip60/Ep400 chromatin remodeling complex severely affects carbohydrate and amino acid metabolism in cranial neural crest cells. The resulting decrease in protein synthesis, proliferation and survival leads to a drastic reduction of cranial neural crest cells early in fetal development and a loss of most facial structures in the absence of either protein. Following heterozygous loss of Kat5 in neural crest cells palatogenesis was impaired. These findings point to a decisive role of the Tip60/Ep400 chromatin remodeling complex in facial morphogenesis and lead us to conclude that the orofacial clefting observed in patients with heterozygous KAT5 missense mutations is at least in part due to disturbances in the cranial neural crest.

Cresta neural, cuarta hoja, germinativa embrionaria / Neural crest, fourth embryonary germinative leaf

RESUMEN Las células de la cresta neural son pluripotenciales y son llamadas la cuarta hoja germinativa del embrión. Con el objetivo de estructurar los referentes teóricos actualizados que sustenten la afirmación precedente y que constituirá material de estudio para los estudiantes de las Ciencias Médicas, se realizó la revisión de 28 referencias bibliográficas, de ellas 89% actualizadas. Estas células aparecen durante la neurulación y pasado este proceso transitan de epitelial a mesenquimatosa; migran siguiendo señales de la matriz extracelular a todo el cuerpo del embrión diferenciándose en tejidos disimiles. Muy vinculados en su evolución a mecanismos epigenéticos, hacen a esta población celular vulnerables a ser dañadas invocándose en la etiología de diferentes defectos congénitos y enfermedades crónicas no trasmisibles como cáncer. Como conclusión por su pluripotencialidad y por los mecanismos moleculares que distinguen su evolución son consideradas por muchos autores la cuarta hoja germinativa del embrión (AU).

SUMMARY Neural crest cells are pluripotentials, and are called the fourth germinative leaf of the embryo. With the objective of structuring the updated theoretical referents backing up the precedent affirmation that will be study material for the students of Medical Sciences, the authors reviewed 28 bibliographic references, 89 % of them updated. These cells appear during neurulation and after this process they transit from epithelial to mesenchymal; following extracellular matrix signals, they migrate to the whole embryo body differentiating themselves in dissimilar tissues. Tightly related in their evolution to epigenetic mechanisms, this cell population is very likely to be damaged and so they are invoked in the etiology of different congenital defects and noncommunicable chronic diseases like cancer. In conclusion, due to their pluripotentiality and the molecular mechanisms distinguishing their evolution, many authors consider them the embryo´s fourth germinative leaf (AU).

A Case of Incidental Retroperitoneal Ganglioneuroma

Ganglioneuroma is a rare benign tumor originating from the neural crest cells. It occurs most commonly in the retroperitoneum and posterior mediastinum and is often found in the neck or pelvis. It may be detected incidentally or detected by pressure effects on the adjacent structures due to its slow growth. However, some functional tumors may secrete catecholamines and present with some clinical symptoms. Complete surgical excision is the treatment of choice. We describe here a case of a retroperitoneal ganglioneuroma which was removed completely by surgery. We review the literature and discuss the clinical features of a ganglioneuroma.

Pathogenic genes and clinical therapeutic strategies for Treacher Collins syndrome / 华西口腔医学杂志

Treacher Collins syndrome is a congenital craniofacial malformation with autosomal dominant inheritance as the main genetic pattern. In this condition, the biosynthesis of ribosomes in neural crest cells and neuroepithelial cells is blocked and the number of neural crest cells that migrate to the craniofacial region decreases, causing first and second branchial arch dysplasia. Definite causative genes include treacle ribosome biogenesis factor 1 (tcof1), RNA polymerase Ⅰ and Ⅲ subunit C (polr1c), and RNA polymerase Ⅰ and Ⅲ subunit D (polr1d). This paper provides a review of research of three major patho-genic genes, pathogenesis, phenotypic research, prevention, and treatment of the syndrome.

La singularidad de los maxilares dentro del sistema esquelético / Singularity of the jaws within the skeletal system

En la odontología es frecuente que se describa la peculiaridad de los huesos maxilares en cuanto a la resistencia a las infecciones en comparación con otros huesos de la economía. O que se plantée un desafío cuando es necesario tomar una decisión acerca de aplicar diferentes conductas terapéuticas en pacientes con patologías óseas sistémicas. Por ello, esta actualización tuvo como objetivo realizar una revisión de la bibliografía para integrar y evidenciar las diferencias y similitudes entre los diferentes huesos de la economía haciendo hincapié en los huesos maxilares. Si bien éstos poseen una gran cantidad de similitudes con el resto de los huesos, también presentan diferencias que los hacen entidades únicas dentro del sistema esquelético como el origen embriológico en las células de las crestas neurales, su alta tasa de remodelación, sin olvidar que estos huesos alojan a órganos que poseen una parte de su estructura en el medio interno y otra porción en medio externo de la cavidad bucal: las piezas dentarias (AU)

Embryological Consideration of Dural AVFs in Relation to the Neural Crest and the Mesoderm / 신경중재치료의학

Intracranial and spinal dural arteriovenous fistulas (DAVFs) are vascular pathologies of the dural membrane with arteriovenous shunts. They are abnormal communications between arteries and veins or dural venous sinuses that sit between the two sheets of the dura mater. The dura propria faces the surface of brain, and the osteal dura faces the bone. The location of the shunt points is not distributed homogeneously on the surface of the dural membrane, but there are certain areas susceptible to DAVFs. The dura mater of the olfactory groove, falx cerebri, inferior sagittal sinus, tentorium cerebelli, and falx cerebelli, and the dura mater at the level of the spinal cord are composed only of dura propria, and these areas are derived from neural crest cells. The dura mater of the cavernous sinus, transverse sinus, sigmoid sinus, and anterior condylar confluence surrounding the hypoglossal canal are composed of both dura propria and osteal dura; this group is derived from mesoderm. Although the cause of this heterogeneity has not yet been determined, there are some specific characteristics and tendencies in terms of the embryological features. The possible reasons for the segmental susceptibility to DAVFs are summarized based on the embryology of the dura mater.

Prenatally detected thoracic neuroblastoma

Neuroblastoma is the most common pediatric extracranial solid tumor derived from primitive neural crest cells of the sympathetic nervous system. Although one-fifths of all neuroblastomas occurs within the thorax, thoracic neuroblastomas detected in fetus have been rarely reported. We report a case of fetal thoracic neuroblastoma with massive pleural effusion detected with prenatal ultrasonography. A 34-year-old Korean second-gravida was referred to our hospital at 30 weeks of gestation for evaluation, after the right lung mass found in the fetus. Approximately 3 cm, well-defined, hyperechoic mass was found in the right thorax with right pleural effusion, with the initial suspicion of teratoma. However, as mass continued to grow with deteriorating pleural effusion and fetal hydrops, the mass was considered malignant after 3 weeks. After a cesarean delivery, an approximately 4 cm mass with peripheral calcification and hemothorax was found on neonatal ultrasonography. Neuroblastoma was diagnosed on excision biopsy.

Immunohistochemistry: sole tool in diagnosing a rare case of primary vaginal amelanotic melanoma

We report a rare case of vaginal amelanotic melanoma. Malignant melanomas are cutaneous and extracutaneous tumors that arise from embryological remnants of neural crest cells/melanocytes. Amelanotic melanomas at such rare locations can be misdiagnosed both clinically and radiologically. Therefore, histopathological examination and immunohistochemistry are mandatory for the diagnosis of these tumors. We diagnosed this case using histopathology and confirmed the diagnosis based on the presence of immunohistochemical markers human melanoma black 45 (HMB45) and S-100.

Research advances in the mechanism of congenital heart disease induced by pregestational diabetes mellitus / 中国当代儿科杂志

Congenital heart disease (CHD) is the most common birth defect at present and has a complex etiology which involves the combined effect of genetic and environmental factors. Pregestational diabetes mellitus is significantly associated with the development of CHD, but the detailed mechanism remains unknown. This article reviews the research advances in the molecular mechanism of CHD caused by pregestational diabetes mellitus.

In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells from Jawbone Compared with Dental Tissue

Autologous bone transplantation is the current gold standard for reconstruction of jawbone defects. Bone regeneration usingmesenchymal stem cells (MSC) is an interesting alternative to improve the current techniques,which necessitate a second site of surgery resulting in donor site morbidity. In this study,we compared the osteogenic ability of jawboneMSC(JB-MSC) withMSC from tissues with neural crest origin, namely, the dental pulp, apical papilla and periodontal ligament. All four types ofMSC were isolated from the same patient (n = 3 donors) to exclude inter-individual variations.TheMSCgrowth and differentiation properties were characterized. The osteogenic differentiation potential in each group of cells was assessed quantitatively to determine if there were any differences between the cell types. All cells expressed the MSC-associated surface markers CD73, CD90, CD105, and CD146 and were negative for CD11b, CD19, CD34, CD45 and HLA-DR. All cell types proliferated at similar rates, exhibited similar clonogenic activity and could differentiate into adipocytes and osteoblasts. An alkaline phosphatase assay, OsteoImage™ assay for mineralization and qRT-PCR measuring the genes runx2, ALP and OCN, indicated that there were no significant differences in the osteogenic differentiation ability between the variousMSCs. In conclusion,we show that from a small segment of jawbone it is possible to isolate sufficient quantities of MSC and that these cells can easily be expanded and differentiated into osteoblasts. JB-MSC appear to be good candidates for future bone regeneration applications in the craniofacial region.

Clinical Features and Treatment Outcome of Soft Tissue Clear Cell Sarcoma / 임상소아혈액종양

BACKGROUND: Soft tissue clear cell sarcoma is a rare tumor which originates from neural crest cells. Due to its rarity and lack of established treatment, the prognosis of clear cell sarcoma is poor. Here, we reviewed the clinical data and outcome of patients diagnosed with soft tissue clear cell sarcoma in our institution.METHODS: A retrospective study was conducted on pediatric patients who were treated for pathologically confirmed soft tissue clear cell sarcoma at the Seoul National University Hospital, between January 2000 and July 2017.RESULTS: Six patients (3 boys and 3 girls) were diagnosed with soft tissue clear cell sarcoma at a median age of 14 years 4 months (range 11 years 7 months - 19 years 3 months). The median size of the tumor was 5.6 cm (range, 0.6 cm to 7.9 cm). The most frequent symptom was pain (67%), and the most common primary site was the lower limb (67%). Three patients (50%) presented with metastases at diagnosis. Four patients underwent chemotherapy with various therapeutic combinations. Four patients received surgical resection. Only one patient received local radiotherapy. One patient died of primary refractory disease, three patients relapsed, while the remaining two survive event-free.CONCLUSION: Soft tissue clear cell sarcoma is a rare and highly aggressive tumor, for which there is no established treatment. All surviving patients received surgery, indicating that surgery is a key treatment modality. Further genetic studies of soft tissue clear cell sarcoma are needed to find a better treatment strategy.

Malignant Paraganglioma in the Common Hepatic Duct / 대한내과학회지

Paragangliomas are rare extra-adrenal neoplasms of neural crest origin. The neoplasms may develop at various sites, but most are located in the para-aortic space along the sympathetic chain. A paraganglioma in the bile duct is very rare; only four cases of such tumors in the hepatic bile duct have been reported to date. Herein, we report on the first Korean case of a malignant paraganglioma in the common hepatic duct (with hepatic metastases) in a 75-year-old male. Computed tomography of the abdomen revealed a heterogeneously enhancing lesion in the common hepatic duct with dilatation of the intrahepatic ducts. After balloon sweeping, the mass exited spontaneously through the Ampulla of Vater. The mass was about 1.5 × 1.3 × 0.5 cm in its dimensions and the surface appeared to be necrotic and edematous. Microscopically, the tumor cells were arranged in a Zellballen pattern. The tumor was diagnosed as a malignant paraganglioma.

Giant Ganglioneuroma of Thoracic Spine: A Case Report and Review of Literature

Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found in the abdomen, but may occasionally present at uncommon sites including the cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely rare. In this report, we describe a 12-year-old girl with giant GN in the thoracic spine, who underwent successful resection (T1–4 level) of the tumor. Histopathological examination confirmed the diagnosis. GN should be considered in the differential diagnosis of any paraspinal mass. A high index of suspicion and correlation of clinico-radiological findings is necessary in differentiating a large benign tumor from a malignant growth. Complete surgical excision is the treatment of choice; however tumor size and location need to be considered for the surgical approach (one-step or multiple surgeries). Close follow-up after surgery is mandatory.

Clinical Features and Treatment Outcome of Soft Tissue Clear Cell Sarcoma / 임상소아혈액종양

BACKGROUND: Soft tissue clear cell sarcoma is a rare tumor which originates from neural crest cells. Due to its rarity and lack of established treatment, the prognosis of clear cell sarcoma is poor. Here, we reviewed the clinical data and outcome of patients diagnosed with soft tissue clear cell sarcoma in our institution. METHODS: A retrospective study was conducted on pediatric patients who were treated for pathologically confirmed soft tissue clear cell sarcoma at the Seoul National University Hospital, between January 2000 and July 2017. RESULTS: Six patients (3 boys and 3 girls) were diagnosed with soft tissue clear cell sarcoma at a median age of 14 years 4 months (range 11 years 7 months - 19 years 3 months). The median size of the tumor was 5.6 cm (range, 0.6 cm to 7.9 cm). The most frequent symptom was pain (67%), and the most common primary site was the lower limb (67%). Three patients (50%) presented with metastases at diagnosis. Four patients underwent chemotherapy with various therapeutic combinations. Four patients received surgical resection. Only one patient received local radiotherapy. One patient died of primary refractory disease, three patients relapsed, while the remaining two survive event-free. CONCLUSION: Soft tissue clear cell sarcoma is a rare and highly aggressive tumor, for which there is no established treatment. All surviving patients received surgery, indicating that surgery is a key treatment modality. Further genetic studies of soft tissue clear cell sarcoma are needed to find a better treatment strategy.

Condition medium of cerebrospinal fluid and retinoic acid induces the transdifferentiation of human dental pulp stem cells into neuroglia and neural like cells / 대한해부학회지

Cerebrospinal fluid (CSF) contains several molecules which are essential for neurogenesis. Human dental pulp stem cells (hDPSCs) are putatively neural crest cell-derived that can differentiate into neurons and glial cells under appropriate neurotrophic factors. The aim of this study was to induce differentiation of hDPSCs into neuroglial phenotypes using retinoic acid (RA) and CSF. The hDPSCs from an impacted third molar were isolated by mechanical and digestion and cultured. The cells have treated by 10⁻⁷µM RA (RA group) for 8 days, 10% CSF (CSF group) for 8 days and RA with CSF for 8 days (RA/CSF group). Nestin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein immunostaining were used to examine the differentiated cells. Axonal outgrowth was detected using Bielschowsky's silver impregnation method and Nissl bodies were stained in differentiated cells by Cresyl violet. The morphology of differentiated cells in treated groups was significantly changed after 3–5 days. The results of immunocytochemistry showed the presence of neuroprogenitor marker nestin was seen in all groups. However, the high percentage of nestin positive cells and MAP2, as mature neural markers, were observed at the pre-induction and induction stage, respectively. Nissl bodies were detected as dark-blue particles in the cytoplasm of treated cells. Our findings showed the RA as pre-inducer and CSF as inducer for using in vitro differentiation of neuron-like cells and neuroglial cells from hDPSCs.

Células de la cresta neural y su relación con cardiopatía congénita: revisión sistemática de la literatura / Neural crest cells and their relation to congenital heart disease: systematic review of the literature

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.

Retinoic acid signal pathway regulation of zebra fish tooth development through manipulation of the differentiation of neural crest / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of retinoic acid (RA) signal in dental evolution, RA is used to explore the influence of the mechanism on neural crest's migration during the early stage of zebra fish embryos.</p><p><b>METHODS</b>We divided embryos of wild type and transgenic line zebra fish into three groups. 1 x 10(-7) to 6 x 10(-7) mol x L(-1) RA and 1 x 10(-7) mo x L(-1) 4-diethylaminobenzaldehyde (DEAB) were added into egg water at 24 hpf for 9 h. Dimethyl sulfoxid (DMSO) with the concentration was used as control group. Then, antisense probes of dlx2a, dlx2b, and barxl were formulated to perform whole-mount in situ hybridization to check the expressions of the genes in 48 hpf to 72 hpf embryos. We observed fluorescence of transgenic line in 4 dpf embryos.</p><p><b>RESULTS</b>We obtained three mRNA probes successfully. Compared with DMSO control group, a low concentration (1 x 10(-7) mol x L(-1)) of RA could up-regulate the expression of mRNA (barx1, dlx2a) in neural crest. Obvious migration trend was observed toward the pharyngeal arch in which teeth adhered. Transgenic fish had spreading fluorescence tendency in pharyngeal arch. However, a high concentration (4 x 10(-7) mol x L(-1)) of RA malformed the embryos and killed them after treatment. One third of the embryos of middle concentration (3 x 10(-7) mo x L(-1)) exhibited delayed development. DEAB resulted in neural crest dysplasia. The expression of barxl and dlx2a were suppressed, and the appearance of dlx2b in tooth was delayed.</p><p><b>CONCLUSION</b>RA signal pathway can regulate the progenitors of tooth by controlling the growth of the neural crest and manipulating tooth development</p>

Understanding of Human Embryo Development for Teratogen Counselling

Human embryology is the study of development from a single cell to a baby in 9 months. Implantation occurs at the end of the first week of development. The second week of development is known as the week of 2's. Gastrulation, the most characteristic event occurring in the third week, establishes three germ layers composed of ectoderm, mesoderm, and endoderm. The three germ layers and neural crest cells lead to the development of their own tissues and organs during the embryonic period, which extends from the third to the eighth week. Major congenital malformations occur in the embryonic period. The fetal period, from the third month to the day of birth, is the time for maturation of tissues and organs, and growth of the body. Because of the close relationship between embryology and congenital abnormalities, knowledge of human development is essential to assess the effects on the embryo when the mother has been exposed to teratogens. This paper briefly reviews the normal embryonic development and associated congenital malformation.

Is there a relationship between complaints of impaired balance and postural control disorder in community-dwelling elderly women? A cross-sectional study with the use of posturography

Background: Risk of falls increases as age advances. Complaints of impaired balance are very common in the elderly age group. Objectives: The objective of this study was to investigate whether the subjective perception of impaired balance was associated with deficits in postural control (objective analysis) in elderly community-dwelling women. Method: Static posturography was used in two groups: elderly women with (WC group) and without (NC group) complaints of impaired balance. The area, mean sway amplitude and mean speed of the center of pressure (COP) in the anterior-posterior (AP) and medial-lateral (ML) directions were analyzed in three stances: single-leg stance, double-leg stance and tandem stance, with eyes open or closed on two different surfaces: stable (firm) and unstable (foam). A digital chronometer was activated to measure the time limit (Tlimit) in the single-leg stance. Kruskal-Wallis tests followed by Mann-Whitney tests, Friedman analyses followed by post hoc Wilcoxon tests and Bonferroni corrections, and Spearman statistical tests were used in the data analysis. Differences of p<0.05 were considered statistically significant. Results: The results of posturography variables revealed no differences between groups. The timed single-leg stance test revealed a shorter Tlimit in the left single-leg stance (p=0.01) in WC group compared to NC group. A negative correlation between posturography variables and Tlimit was detected. Conclusions: Posturography did not show any differences between the groups; however, the timed single-leg stance allowed the authors to observe differences in postural control performance between elderly women with and those without complaints of impaired balance. .