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Transcriptional disruption in craniofacial neural crest by administration of drugs at the early stage of pregnancy possibly causes the HFM-like craniofacial malformation in rat embryos.

妊娠早期给药导致颅面神经嵴转录破坏，可能导致大鼠胚胎出现 HFM 样颅面畸形。

基本信息

批准号：
21K10261
负责人：
今井元
金额：
$ 2.66万
依托单位：
Ohu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

本研究の作業目標は、『① 頭部神経堤の上皮間葉転換/脱上皮化(EMT)が、どのように阻害されるのか。② 頭部NCCの移動経路が、どのように攪乱されるのか。③脳神経の軸索ガイダンス因子が、どのように攪乱されるのか。④脳神経ニューロンの伸長が、どのように攪乱されるのか。⑤ 上顎・下顎・舌骨・耳小骨などに、どのような奇形を生じるのか。』などである。今年度は、推定受精時刻に個体差が大きかったSDラットから、受精時刻に個体差が殆ど生じないWistar-Imamichi ラットに系統を変え、目的とする発生ステージの胎仔を確実に得られる時刻を確定した。すなわち、同じ繁殖元から購入したWistar-Imamichi ラットにおける妊娠日齢・時刻とsomite（体節）数の関係を明らかにし、これによって、今までのSDラットの実験系では限界があった、胎仔の厳密な発生ステージ特異的なVPA投与の影響を、同じ発生ステージにある胎仔のサンプル数を揃えて解析することが可能になった。既に、上記の『⑤ 上顎・下顎・舌骨・耳小骨などに、どのような奇形を生じるのか。』に対する研究を進めている。すなわち、妊娠8日目のWistar-Imamichiラットの母獣 (胎仔の胎齢8.75：頭部神経堤形成期の直前に相当)を用いて、実験群にはVPA、対照群には生理食塩水を単回投与し、頭部NCCの形成と移動の撹乱を行った胚を妊娠20日目に摘出し、アルシアンブルー-アリザリンレッド染色をした透明化骨格標本を作成し、これらのサンプルの解析を進めている最中である。

The objective of this study was: ① Epithelial-mesenchymal transformation/deepithelialization (EMT) of the cerebral cortex and the prevention of damage. 2. The head NCC moves along the path, and the head NCC moves along the path. 3. The axis of the nervous system is divided into two parts: the axis of the nervous system is divided into three parts: the axis of the nervous system is divided into four parts: the axis of the nervous system is divided (4) The extension of the mental state, the change of the mental state, and the change of the mental state. 5 Upper jaw, lower jaw, hyoid bone, ear small bone』などである。This year, the estimated fertilization time of the individual difference is large, the fertilization time of the individual difference is close to the birth of the Wistar-Imamichi system, the purpose of the birth of the fetus is determined. The relationship between the number of somite (body segment) and the number of Wistar-Imamichi (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) and the number of Wistar-Imamichi (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) of the same reproductive element and the number of somite (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) of the same reproductive element and the number of somite (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) of the same reproductive element and the number of somite (body segment) of somite (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) of the same reproductive element and the number of somite (body segment) of the same reproductive element is clearly defined. The relationship between the number of somite (body segment) of the same reproductive element and the number of somite (body segment) of the The upper jaw, the lower jaw, the hyoid bone, the ear bone, the strange shape, the strange shape. The study was carried out in a timely manner.すなわち、妊娠8日目のWistar-Imamichiラットの母獣(Fetus 8.75: The period of formation of the cranial nervous system is equivalent to the period before). In the middle of the pregnancy, the VPA of the group, the physiological water of the group, the formation and movement of the NCC of the head, the disturbance of the embryo, the extraction of the embryo on the 20th day of pregnancy, the disappearance of the dye, the preparation of the transparent bone structure, the analysis of the progress of the group.