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가민한
가민한 (Minhan Ka) 저자 이메일 보기
University of Nebraska Medical Center
 
조회 265  인쇄하기 주소복사 트위터 공유 페이스북 공유 
ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway
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Abstract
Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.

Keywords : ANKRD11, Dendrite, Arborization, Dendritic spine, TrkB, BDNF, Histone acetylation, Autism, Intellectual disability
논문정보 F1000선정
- 형식: Research article
- 게재일: 2018년 03월 (BRIC 등록일 2018-10-23)
- 연구진: 국외연구진
- 분야: Neuroscience
- 추천: Faculty of 1000 Biology
- 추천사유: Gupton S and Menon S: F1000Prime Recommendation of [Ka M and Kim WY, Neurobiol Dis 2018 111:138-152]. In F1000Prime, 22 Oct 2018; 10.3410/f.732360190.793552038
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Neuroscience

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Google (by Minhan Ka)
Pubmed (by Minhan Ka)
프리미엄 Bio일정 Bio일정 프리미엄 안내
2018 Ajou Biomedical International Symposium / Genoproteomic Signature of Human Diseases
2018 Ajou Biomedical International Symposium / Genoproteomic Signature of Human Diseases
날짜: 2018.11.26
장소: 아주대학교의료원 별관 대강당 (수원)
Human Genome Meeting 2019
Human Genome Meeting 2019
초록접수: ~2018.12.31
사전접수: ~2018.12.31
날짜: 2019.04.24~26
장소: 이화여자대학교 삼성홀
International Forum on Medical Innovation of Cell & Bio Therapy
International Forum on Medical Innovation of Cell & Bio Therapy
사전접수: ~2018.11.21
날짜: 2018.11.23
장소: 서울대학교병원 의생명연구원 1층 강당(대학로 소재)
[K-Genome Symposium 2018] 유전체, 헬스빅데이터, 그리고 정밀의료
[K-Genome Symposium 2018] 유전체, 헬스빅데이터, 그리고 정밀의료
날짜: 2018.11.19
장소: 아주대학교의료원 별관 대강당
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