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Morphological study of embryonic Chd8+/- mouse brains using light-sheet microscopy
bioRxiv - Developmental Biology Pub Date : 2020-10-05 , DOI: 10.1101/2020.10.05.326132
Harold F. Gómez , Leonie Hodel , Odyssé Michos , Dagmar Iber

Objective: Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental conditions that remain poorly understood due to their genetic complexity. CHD8 is a risk allele strongly associated with ASD, and heterozygous Chd8 loss-of-function mice have been reported to exhibit macrocephaly in early postnatal stages. In this work, we sought to identify measurable brain alterations in early embryonic development. Results: We performed light-sheet fluorescence microscopy imaging of N-cadherin stained and optically cleared Chd8+/- and wild-type mouse brains at embryonic day 12.5 (E12.5). We report a detailed morphometric characterization of embryonic brain shapes and cortical neuroepithelial apical architecture. While Chd8+/- characteristic expansion of the forebrain and midbrain was not observed this early in embryogenesis, a tendency for a decreased lateral ventricular sphericity and an increased intraocular distance in Chd8+/- brains was found compared to controls. This study advocates the use of high-resolution microscopy technologies and multi-scale morphometric analyses of target brain regions to explore the etiology and cellular basis of Chd8 haploinsufficiency.

中文翻译:

利用光片显微镜观察胚胎Chd8 +/-小鼠大脑的形态

目的:自闭症谱系障碍(ASD)涵盖了由于其遗传复杂性而仍被人们广泛了解的一组神经发育疾病。CHD8是与ASD密切相关的风险等位基因,据报道杂合的Chd8功能丧失的小鼠在出生后早期表现出大头畸形。在这项工作中,我们试图确定早期胚胎发育中可测量的大脑改变。结果:我们在胚胎第12.5天(E12.5)对N-钙黏着蛋白染色并光学清除的Chd8 +/-和野生型小鼠大脑进行了光片荧光显微镜成像。我们报告了胚胎脑的形状和皮质神经上皮根尖结构的详细形态计量学表征。尽管在胚胎发生的早期阶段未观察到Chd8 +/-特征性前脑和中脑的扩张,与对照组相比,发现Chd8 +/-大脑的外侧心室球性降低和眼内距离增加的趋势。这项研究提倡使用高分辨率的显微镜技术和目标大脑区域的多尺度形态分析来探索Chd8单倍体功能不全的病因和细胞基础。
更新日期:2020-10-06
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