Flentke George R, Smith Susan M
UNC-Nutrition Research Institute and Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA.
Biochem Cell Biol. 2018 Apr;96(2):98-106. doi: 10.1139/bcb-2017-0205. Epub 2017 Oct 12.
Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chicken (Gallus gallus domesticus) is a powerful embryological research model, and was possibly the first in which the teratogenicity of alcohol was demonstrated. Pharmacologically relevant exposure to alcohol in the range of 20-70 mmol/L (20-80 mg/egg) disrupt the growth of chicken embryos, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models. The avian embryo's direct accessibility has enabled novel insights into the teratogenic mechanisms of alcohol. These include the contribution of IGF1 signaling to growth suppression, the altered flow dynamics that reshape valvuloseptal morphogenesis and mediate its cardiac teratogenicity, and the suppression of Wnt and Shh signals thereby disrupting the migration, expansion, and survival of the neural crest, and underlie its characteristic craniofacial deficits. The genetic diversity within commercial avian strains has enabled the identification of unique loci, such as ribosome biogenesis, that modify vulnerability to alcohol. This venerable research model is equally relevant for the future, as the application of technological advances including CRISPR, optogenetics, and biophotonics to the embryo's ready accessibility creates a unique model in which investigators can manipulate and monitor the embryo in real-time to investigate the effect of alcohol on cell fate.
产前酒精暴露（PAE）仍然是结构性出生缺陷和永久性神经发育残疾的主要可预防原因。鸡（家鸡）是一种强大的胚胎学研究模型，可能是首个证明酒精致畸性的动物模型。药理学相关剂量的酒精，浓度范围为20 - 70 mmol/L（20 - 80 mg/蛋），会干扰鸡胚胎的生长、形态发生和行为，所产生的表型与哺乳动物模型的表型高度相似。禽类胚胎的直接可及性为酒精致畸机制带来了新的见解。这些机制包括胰岛素样生长因子1（IGF1）信号传导对生长抑制的作用、重塑瓣膜间隔形态发生并介导其心脏致畸性的血流动力学改变，以及Wnt和Shh信号的抑制，从而破坏神经嵴的迁移、扩展和存活，并导致其典型的颅面缺陷。商业禽类品系中的遗传多样性使得能够识别独特的基因座，如核糖体生物发生相关基因座，这些基因座会改变对酒精的易感性。这个古老的研究模型在未来同样具有重要意义，因为将包括CRISPR、光遗传学和生物光子学在内的技术进步应用于易于操作的胚胎，创建了一个独特的模型，研究人员可以在其中实时操纵和监测胚胎，以研究酒精对细胞命运的影响。
