Craniofacial Morphogenesis in Prenatal Alcohol Exposure

产前酒精暴露中的颅面形态发生

• 批准号: 10025955
• 负责人: SUSAN M. SMITH
• 金额: $ 3.91万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10025955
• 关键词: Address; Affect; Alcohols; Apoptosis; Apoptotic; Award; Calcium; Cells; Characteristics; Data Set; Doctor of Philosophy; Dysmorphology; Embryonic Development; Epigenetic Process; Exons; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Genetic Polymorphism; Human; Individual; Investigation; Knowledge; Lactation; Mediating; MicroRNAs; Morphogenesis; Mus; Neural Crest; Neurodevelopmental Disability; Parents; Positioning Attribute; Ribosomes; Role; Signal Transduction; Stress; Structure; Testing; Training; Vertebrates; alcohol response; base; career; craniofacial; embryo/fetus; nerve stem cell; progenitor; stem cell population; stem cells; transcriptome; zinc-binding protein

ABSTRACT Prenatal alcohol exposure is a leading cause of neurodevelopmental disability and may be accompanied by characteristic facial deficits caused, in part, by the apoptotic deletion of neural crest progenitor cells. The parent R01 (AA011085) tests the hypothesis that ribosome dysbiogenesis and nucleolar stress drive this apoptosis, based on our whole transcriptome analysis of these cells. Exon-level reanalysis of that dataset uncovered 19 miRNAs having altered representation in response to alcohol. One of these, miR- 3064-3p, is induced by alcohol (Fold-change 1.55, p=0.0002). miR-3064 is conserved across vertebrates and is implicated in our ribosome dysbiogenesis and calcium-mediated apoptosis. Dr. Olivia Rivera joined my lab July 22, 2019 to obtain training in epigenetics, and how alcohol dysregulates epigenetic signals to impede embryo development. Her Ph.D. identified a polymorphism in a zinc transporter that affects lactation in human and mouse. Upon discussion, we determined that investigation into miR- 3064’s role in neural crest apoptosis addresses this training, represents a logical extension of the parent award, and positions Dr. Rivera for an independent career in alcohol and epigenetics.

摘要 产前酒精暴露是神经发育障碍的主要原因，并可能伴随 特征面部缺陷，部分是由于神经脊祖细胞的凋亡缺失引起的。 亲本R01(AA011085)验证了核糖体失调和核仁应激驱动的假说 这种细胞凋亡，基于我们对这些细胞的整个转录组分析。外显子水平的重新分析 数据集发现了19个miRNAs对酒精的反应改变了表达。其中之一，mir- 3064-3P为酒精所致(折变率1.55，p=0.0002)。MIR-3064在脊椎动物中是保守的 并与我们的核糖体失调和钙介导的细胞凋亡有关。奥利维亚·里维拉医生 2019年7月22日加入我的实验室，接受表观遗传学以及酒精如何失调表观遗传学的培训 阻碍胚胎发育的信号。她的博士发现了一种锌转运蛋白的多态 影响人和小鼠的哺乳期。经过讨论，我们决定对MIR- S在神经峰细胞凋亡中的作用解决了这种训练，代表了亲本的逻辑延伸 获奖，并为里维拉博士在酒精和表观遗传学领域的独立职业生涯奠定了基础。