Ethanol exposure perturbs sea urchin development and disrupts developmental timing
Ethanol exposure perturbs sea urchin development and disrupts developmental timing
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DOI：
10.1016/j.ydbio.2022.11.001
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发表时间：
2022-11-18
影响因子：
2.7
通讯作者：
Bradham，Cynthia A.
中科院分区：
文献类型：
--
作者：
Rodriguez-Sastre，Nahomie;Shapiro，Nicholas;Bradham，Cynthia A.
乙醇是一种已知的脊椎动物致畸物，作为胎儿酒精综合征（FAS）的一个组成部分，它会导致颅面缺陷。我们的研究结果表明，用乙醇处理的海胆胚胎同样表现出广泛的骨骼模式缺陷，可能类似于与FAS相关的缺陷。海胆幼体骨架是一个简单的模式系统，只涉及两种细胞类型：分泌碳酸钙骨架的原代间充质细胞（PMCs）和为PMCs提供迁移、定位和分化线索的外胚层细胞。RA生物合成和Hh信号通路的扰动被认为是脊椎动物FAS表型的原因。令人惊讶的是，我们的结果表明，这些途径在功能上与乙醇对发育中的海胆的致畸作用无关。我们发现乙醇暴露延迟了发育形态以及一些外胚层和PMC基因的表达。时间转录组分析揭示了乙醇对信号传导和代谢基因表达的显著影响，以及GRN基因表达时间的中断，包括整个规范网络中的延迟和早熟基因表达。我们得出结论，乙醇处理胚胎的骨骼模式扰动可能是由于指导组织和反应组织内部和之间的时间同步丧失。
Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal alcohol syndrome (FAS). Our results show that sea urchin embryos treated with ethanol similarly show broad skeletal patterning defects, potentially analogous to the defects associated with FAS. The sea urchin larval skeleton is a simple patterning system that involves only two cell types: the primary mesenchymal cells (PMCs) that secrete the calcium carbonate skeleton and the ectodermal cells that provide migratory, positional, and differentiation cues for the PMCs. Perturbations in RA biosynthesis and Hh signaling pathways are thought to be causal for the FAS phenotype in vertebrates. Surprisingly, our results indicate that these pathways are not functionally relevant for the teratogenic effects of ethanol in developing sea urchins. We found that developmental morphology as well as the expression of some ectodermal and PMC genes was delayed by ethanol exposure. Temporal transcriptome analysis revealed significant impacts of ethanol on signaling and metabolic gene expression, and a disruption in the timing of GRN gene expression that includes both delayed and precocious gene expression throughout the specification network. We conclude that the skeletal patterning perturbations in ethanol-treated embryos likely arise from a loss of temporal synchrony within and between the instructive and responsive tissues.