Developmental mechanisms of sebaceous nevus syndrome caused by dysregulation of RAS/MAPK pathway.
- Developmental mechanisms of sebaceous nevus syndrome caused by dysregulation of RAS/MAPK pathway.
- BAEK, SEUNG TAE; KIM, YE EUN
- Date Issued
- Sebaceous nevus syndrome is a neuro-cutaneous disorder that shows neurological symptoms such as epilepsy, mental retardation, cerebral defect and ocular abnormality with the skin lesion called nevus sebaceous. Recently, it has been reported that sebaceous nevus syndrome is caused by somatic mutation of KRAS and HRAS during development. Interestingly, other neurodevelopmental conditions that are associated with genetic mutations in the components of RAS/MAPK pathway also show characteristic neurological symptoms including mental retardation, epilepsy, seizures, and learning disability which may explained by perturbation of RAS/MAPK pathway. We found that the mis-activation of RAS/MAPK pathway resulted in neurological defects associated with sebaceous nevus syndrome. Activation of RAS/MAPK pathway by ectopic over-expression of KRAS p.G12V in developing mouse brain caused severe migration defects and abnormal differentiation. To further demonstrate how constitutive activation of KRAS leads these neurodevelopmental defect, we will investigate the relationship between RAS/MAPK pathway and these defects using co-staining with pERK and pharmacological way. We will also identify the disease-related cellular phenotype and characterize the gene expression profile by using human embryonic stem cell-derived neuronal progenitor cells. These data may explain underlying molecular mechanisms of neurodevelopmental defects caused by the mis-regulation of RAS/MAPK pathway.
- Article Type
- IBRO 2019, 2019-09-25
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