• BMB Reports
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• 제55권5호
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• pp.232-237
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• 2022

The Wnt/β-catenin signaling plays crucial roles in early development, tissue homeostasis, stem cells, and cancers. Here, we show that RNF152, an E3 ligase localized to lysosomes, acts as a negative regulator of the Wnt/β-catenin pathway during Xenopus early embryogenesis. Overexpression of wild-type (WT) RNF152 inhibited XWnt8-induced stabilization of β-catenin, ectopic expression of target genes, and activity of a Wnt-responsive promoter. Likewise, an E3 ligase-defective RNF152 had repressive effects on the Wnt-dependent gene responses but not its truncation mutant lacking the transmembrane domain. Conversely, knockdown of RNF152 further enhanced the transcriptional responses induced by XWnt8. RNF152 morphants exhibited defects in craniofacial structures and pigmentation. In line with this, the gain-of-RNF152 function interfered with the expression of neural crest (NC) markers, whereas its depletion up-regulated NC formation in the early embryo. Mechanistically, RNF152 inhibits the polymerization of Dishevelled, which is key to Wnt signaling, in an E3 ligase-independent manner. Together, these results suggest that RNF152 controls negatively Wnt/β-catenin signaling to fine-tune its activity for NC formation in Xenopus embryo.

• 생명과학회지
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• 제18권9호
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• pp.1219-1224
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• 2008

Neural crest는 신경계의 발생과정에서 생긴 특정화된 외배엽으로서 말초신경계(peripheral nervous system)의 모든 sensory cells과 fibers, 자율신경계의 대부분의 peripheral cells, unipolar spinal ganglion cell, cranial sensory ganglia, peripheral nerve의 neurolemmal sheath cells, ganglia의 capsule cells, sympathetic ganglia, chromaffin cells, pigment cell 등이 분화한다. Fish의 경우는 melanin을 가지고 있는 melanophores, yellow pigment를 가지고 있는 xanthopores, reflecting platelets를 가지고 있는 iridophores등 3가지의 pigment-producing cell을 가지고 있다. 다양한 pigement들의 deposition, distribution에 의해 Fish와 amphibian에서 볼 수 있는 수많은 color와 pattern이 만들어지게 된다. Embryonic neural crest가 patterning을 연구하기에 아주 좋은 모델임에도 불구하고, choromatophores의 cell-signaling mechanism에 관한 연구는 거의 없는 실정이다. 본 연구에서는 melanosomes의 melanocyt로의 이동기작과 이들의 dentiritic processe를 밝히기 밝히기 위해 phosphorylaion assay와 투과형 전자 현미경(transmission electron microscope)등을 이용한 다양한 실험들을 토대로, Lithium에 의해 유도되는 morphological alteration에 IP cell signaling pathway에 의해 조절되는 단백질의 하나인 55-kDa단백질의 인산화가 중요한 역할을 함을 밝혔다.

• International Journal of Molecular Medicine
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• 제43권2호
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• pp.1105-1113
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• 2019

Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono- and di-methylated ninth lysine of histone 3 and belongs to the Jumonji domain-containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor-mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small-sized eyes and abnormal pigmentation. Whole-mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.

• 대한소아치과학회지
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• 제24권1호
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• pp.19-26
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• 1997

Odontodysplasia is a rare developmental anomaly of tooth formation in which hard tissue are affected. Odontodyplasia affects the primary and permanent dentitions in the maxilla, mandible, or both jaws. The maxilla is involved twice as often as the mandible. The condition is more common in female than in male patients and in the anterior than in the posterior regions. The clinical manifestation of odontodysplasia are hypoplasia and hypocalcification of the enamel and dentin of affected teeth. Teeth tend to be small and discolored, with short roots and widely open pulp canal. Delayed eruption of affected teeth with abscess formation is common. Radiographically teeth assume a faint radiolucent image ("ghost teeth"). enamel and dentin appear thin and are similar in radiodensity. The pulp chambers are often larger than normal, calcifications(pulp stone and denticle) are found within them. The etiology of regional odontodysplasia is unknown. However, several causes have been discussed, including somatic mutation, local circulatory disorders, local trauma, failure of migration and differentiation of neural crest cells, local infection.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권2호
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• 대한구순구개열학회지
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• 제8권1호
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• pp.23-29
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• 2005

The facial cleft and duplicated maxilla are lire congenital anomaly. After Rushton and Walker had reported a unilateral facial cleft with excess tooth and bone formation in 1937, few authors described similar cases. The etiology of this anomaly is not well understood, but considered embryologically as a neurocristopathy. A neurocristopathy is defined as a condition arising from aberrations in early migration, growth and differentiation of neural crest cells. This aberrations result in facial malformation such as facial clefts and loss or duplication of facial structures. We experienced a male newborn baby with bilateral facial cleft and duplicated maxilla. The cleft was surgically corrected when he was 5 months old. The function and appearance of lip are improved. Duplicated maxilla will be surgically removed. We report this case with review of literatures.

• International Journal of Oral Biology
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• 제36권1호
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• pp.31-35
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• 2011

Teeth develop via a reciprocal induction between the ectomesenchyme originating from the neural crest and the ectodermal epithelium. During complete formation of the tooth morphology and structure, many cells proliferate, differentiate, and can be replaced with other structures. Apoptosis is a type of genetically-controlled cell death and a biological process arising at the cellular level during development. To determine if apoptosis is an effective mechanism for eliminating cells during tooth development, this process was examined in the rat mandible including the developing molar teeth using the transferase-mediated dUTP-biotin nick labeling (TUNEL) method. The tooth germ of the mandibular first molar in the postnatal rat showed a variety of morphological appearances from the bell stage to the crown stage. Strong TUNEL-positive reactivity was observed in the ameloblasts and cells of the stellate reticulum. Odontoblasts near the prospective cusp area also showed a TUNEL positive reaction and several cells in the dental papilla, which are the forming pulp, were also stained intensively in this assay. Our results thus show that apoptosis may take place not only in epithelial-derived dental organs but also in the mesenchyme-derived dental papilla. Hence, apoptosis may be an essential biological process in tooth development.

• The Korean Journal of Pain
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• 제11권1호
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• pp.7-22
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• 1998

The development of the superior cervical ganglion was studied by electron microscopic method in human fetuses ranging from 40 mm to 260 mm of crown-rump length(10 to 30 weeks of gestational age). At 40 mm fetus, the superior cervical ganglion was composed of clusters of undifferentiated cell, primitive neuroblast, primitive supporting cell, and unmyelinated fibers. At 70 mm fetus, the neuroblasts and their processes were ensheated by the bodies or processes of satellite cells. The cytoplasm of the neuroblast contained rough endoplasmic reticulum, mitochondria, Golgi complex, Nissl bodies and dense-cored vesicles. As the neuroblasts grew and differentiated dense-cored vesicles moved away from perikaryal cytoplasm into developing processes. Synaptic contacts between the cholinergic axon and dendrites of postganglionic neuron and a few axosomatic synapses were first observed at 70 mm fetus. At 90 mm fetus the superior cervical ganglion consisted of neuroblasts, satellite cells, granule-containing cells, and unmyelinated nerve fibers. The ganglion cells increased somewhat in numbers and size by 150 mm fetus. Further differentiation resulted in the formation of young ganglion cells, whose cytoplasm was densely filled with cell organelles. During next prenatal stage up to 260 mm fetus, the cytoplasm of the ganglion cells contained except for large pigment granules, all intracytoplasmic structures which were also found in mature superior cervical ganglion. A great number of synaptic contact zones between the cholinergic preganglionic axon and the dendrites of the postganglionic neuron were observed and a few axosomatic synapses were also observed. Two morphological types of the granule-containing cells in the superior cervical ganglion were first identified at 90 mm fetus. Type I granule-containing cell occurred in solitary, whereas type II tended to appeared in clusters near the blood capillaries. Synaptic contacts were first found on the solitary granule-containing cell at 150 mm fetus. Synaptic contacts between the soma of type I granule-containing cells and preganglionic axon termials were observed. In addition, synaptic junctions between the processes of the granule-containing cells and dendrites of postganglionic neuron were also observed from 150 mm fetus onward. In conclusion, superior cervical ganglion cells and granule-containing cells arise from a common undifferentiated cell precursor of neural crest. The granule-containg cells exhibit a local modulatory feedback system in the superior cervical ganglion and may serve as interneurons between the preganglionic and postganglionic cells.

• 대한장애인치과학회지
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• 제11권1호
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• pp.5-8
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• 2015

다발성 우식증을 주소로 내원한 7세 1개월의 여자아이가 신경모세포종의 다각적 치료에 따른 치근 형성이상으로 인해 하악 영구절치의 중증도 동요도를 보여 mini-screw를 이용한 레진강선고정을 시행하였다. 이를 통해 동요도의 감소 및 교합안정을 이루었으며, 따라서 하악 영구절치의 치근 형성이상으로 인한 동요도 증가 시 선택적 치료법이 될 수 있을 것이라 생각한다.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.213-220
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• 2022

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.