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.
Animals ; Mice ; Chromatin Assembly and Disassembly ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; DNA Helicases/metabolism* ; DNA-Binding Proteins ; Neural Crest/metabolism* ; Skull ; Transcription Factors/metabolism*

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.
DNA-Directed RNA Polymerases ; genetics ; Humans ; Mandibulofacial Dysostosis ; genetics ; Neural Crest ; Nuclear Proteins ; Phosphoproteins

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.
Arteries ; Brain ; Cavernous Sinus ; Central Nervous System Vascular Malformations ; Colon, Sigmoid ; Dura Mater ; Embryology ; Membranes ; Mesoderm ; Neural Crest ; Pathology ; Population Characteristics ; Spinal Cord ; Veins

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.
Catecholamines ; Ganglioneuroma ; Mediastinum ; Neck ; Neural Crest ; Pelvis

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.
Adult ; Biopsy ; Fetus ; Hemothorax ; Humans ; Hydrops Fetalis ; Lung ; Mediastinum ; Neural Crest ; Neuroblastoma* ; Pleural Effusion ; Pregnancy ; Sympathetic Nervous System ; Teratoma ; Thorax ; Ultrasonography ; Ultrasonography, Prenatal

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.
Diagnosis ; Humans ; Immunohistochemistry* ; Melanoma ; Melanoma, Amelanotic* ; Neural Crest ; Vagina

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.
Abdomen ; Aged ; Ampulla of Vater ; Bile Ducts ; Dilatation ; Hepatic Duct, Common* ; Humans ; Male ; Neoplasm Metastasis ; Neural Crest ; Paraganglioma*

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.
Animals ; Apoptosis ; Cell Movement ; Female ; Heart Defects, Congenital ; etiology ; Humans ; Neural Crest ; physiology ; Pregnancy ; Pregnancy in Diabetics ; Reactive Oxygen Species ; metabolism

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.
Abdomen ; Child ; Diagnosis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Ganglioneuroma* ; Humans ; Neural Crest ; Spine*

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.
Axons ; Cerebrospinal Fluid* ; Cytoplasm ; Dental Pulp* ; Digestion ; Glial Fibrillary Acidic Protein ; Humans* ; Immunohistochemistry ; In Vitro Techniques ; Methods ; Microtubule-Associated Proteins ; Molar, Third ; Nerve Growth Factors ; Nestin ; Neural Crest ; Neurogenesis ; Neuroglia* ; Neurons ; Nissl Bodies ; Phenotype ; Silver ; Stem Cells* ; Tretinoin* ; Viola