• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.24-25
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• 2003

The zebrafish (Danio rerio) is now the pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. I will talk about positional cloning of two developmental mutants in zebrafish. The first mutant is headless: The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo by virtue of its distinct head and trunk inducing properties. Wingless/Wntantagonists secreted by the organizer have been identified as head inducers. Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling during early gastrulation blocks head formation. These observations suggest that the ability of head inducers to inhibit Wntsignalling during formation of anterior structures is what distinguishes them from trunk inducers that permit the operation of posteriorizing Wnt signals. I describe the zebrafish headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef family. Loss of Tcf3 function in the hdl mutant reveals that hdl represses Wnt target genes. I provide genetic evidence that a component of the Wntsignalling pathway is essential in vertebrate head formation and patterning. Second mutant is mind bomb: Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneuralgene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. (중략)

• Molecules and Cells
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• v.43 no.12
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• pp.1011-1022
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• 2020

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation.

• BMB Reports
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• v.51 no.10
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• Journal of Biomedical Engineering Research
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• v.18 no.3
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• pp.233-241
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• 1997

The research on chromosomes is very significant in cytogenetics since genes of the chromosomes control revelation of the inheritance plasma. The human chromosome analysis is widely used to study leukemia, malignancy, radiation hazard, and mutagen dosimetry as well as various congenital anomalies such as Down's, Klinefelter's, Edward's, and Patau's syndrome. The framing and analysis of the chromosome karyogram, which requires specific cytogenetic knowledge is most important in this field. Many researches on automated chromosome karyotype analysis methods have been carried out, some of which produced commercial systems. However, there still remains much room to improve the accuracy of chromosome classification and to reduce the processing time in real clinic environments. In this paper, we proposed a hierarchical artificial neural network(HANN) to classify the chromosome karyotype. We extracted three or four chromosome morphological feature parameters such as centromeric index, relative length ratio, relative area ratio, and chromosome length by preprocessing from ten human chromosome images. The feature parameters of five human chromosome images were used to learn HANN and the rest of them were used to classify the chromosome images. The experiment results show that the chromosome classification error is reduced much more than that of the other researchers using less feature parameters.

• Journal of Veterinary Science
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• v.22 no.1
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• pp.7.1-7.13
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• 2021

Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

• BMB Reports
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• v.49 no.12
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• pp.671-680
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• 2016

Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

• BMB Reports
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• v.42 no.11
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• pp.705-712
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• 2009

Our understanding of the relationships between genes, brains, and behaviors has changed a lot since the first behavioral mutants were isolated in the fly bottles of the Benzer lab at Caltech (1), but Drosophila is still an excellent model system for studying the neurobiology of behavior. Recent advances provide an unprecedented level of control over fly neural circuits. Efforts are underway to add to existing GAL4-driver lines that permit exogenous expression of genetic tools in small populations of neurons. Combining these driver lines with a variety of inducible UAS lines permits the visualization of neuronal morphology, connectivity, and activity. These driver lines also make it possible to specifically ablate, inhibit, or activate subsets of neurons and assess their roles in the generation of behavioral responses. Here, I will briefly review the extensive arsenal now available to drosophilists for investigating the neuronal control of behavior.

• Proceedings of the Korean Information Science Society Conference
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• 2003.04c
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• pp.359-361
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• 2003

정확한 암의 분류는 암의 진단 및 치료에 있어 매우 중요하지만, 암을 진단하기 위한 기존의 여러 방법들은 종종 불완전한 결과를 도출한다. 최근의 마이크로어레이 기술에 기반한 분자 수준의 진단은 정확하고 객관적이며 체계적인 암의 분류를 위한 방법론을 제시해준다. 유전자 발현 데이터는 일반적으로 수천개 이상의 유전자를 포함하는데, 유전자 발현 데이터의 모든 유전자가 암과 관련이 있는 것이 아니므로 정확한 암을 분류하기 위하여 중요한 유전자만을 추출하는 것이 바람직하다. 본 논문에서 음의 상관관계를 갖는 두 개의 이상적인 유전자 벡터를 정의한 후 이와 유사한 정도를 기준으로 중요한 유전자 집단을 추출하고, 각각을 신경망으로 학습하여 결합하는 신경망 쌍을 제안한다. 실험 결과는 음의 상관관계를 갖는 두 개의 유전자 집단이 암의 클래스를 잘 구분할 수 있음을 보여주었다. 이 유전자 집단을 특징으로 하여 각각 학습한 신경망을 베이시안 방법으로 결합한 결과, 벤치마크 데이터에 대하여 신경망 쌍이 개별 분류기에 비해 우수한 성능을 보임을 확인하였다.

• Advances in pediatric surgery
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• v.14 no.1
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• pp.75-82
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• 2008

Neuroblastoma arises from the primitive neural crest cells, and is a common malignancy in childhood. The clinical features are characterized by biological heterogeneity. Neuronal degeneration and differentiation occur in some patients. However treatment in the high risk group accounting for approximately half, has not been satisfactory despite a multimodal approach. Therefore, effective treatment is determined by the risk group of prognostic factors, such as age at diagnosis, stage of disease, pathological finding and N-myc amplification. Neuroblastoma can be diagnosed prenatally, which suggests its origin during the normal embryogenesis. Recent knowledge of molecular biology, such as Trk genes, and the concept of cancer stem cells have given us some improved understanding on this disease. Currently, targeted therapies based on the molecular biology of neuroblastoma are under investigation and increasing survival rate and decreasing late complications could be appreciated.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.265-271
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• 2019

The expansion and folding of the cerebral cortex occur during brain development and are critical factors that influence cognitive ability and sensorimotor skills. The disruption of cortical growth and folding may cause neurological disorders, resulting in severe intellectual disability and intractable epilepsy in humans. Therefore, understanding the mechanism that regulates cortical growth and folding will be crucial in deciphering the key steps of brain development and finding new therapeutic targets for the congenital anomalies of the cerebral cortex. This review will start with a brief introduction describing the anatomy of the brain cortex, followed by a description of our understanding of the proliferation, differentiation, and migration of neural progenitors and important genes and molecules that are involved in these processes. Finally, various types of disorders that develop due to malformation of the cerebral cortex will be discussed.