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早期发育细胞群体的变异性导致随机性左右不对称缺陷。

Variability of an Early Developmental Cell Population Underlies Stochastic Laterality Defects.

机构信息

Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Hannoversche Strasse 28, 10115 Berlin, Germany.

Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Hannoversche Strasse 28, 10115 Berlin, Germany.

出版信息

Cell Rep. 2021 Jan 12;34(2):108606. doi: 10.1016/j.celrep.2020.108606.

DOI:10.1016/j.celrep.2020.108606
PMID:33440143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7809618/
Abstract

Embryonic development seemingly proceeds with almost perfect precision. However, it is largely unknown how much underlying microscopic variability is compatible with normal development. Here, we quantify embryo-to-embryo variability in vertebrate development by studying cell number variation in the zebrafish endoderm. We notice that the size of a sub-population of the endoderm, the dorsal forerunner cells (DFCs, which later form the left-right organizer), exhibits significantly more embryo-to-embryo variation than the rest of the endoderm. We find that, with incubation of the embryos at elevated temperature, the frequency of left-right laterality defects is increased drastically in embryos with a low number of DFCs. Furthermore, we observe that these fluctuations have a large stochastic component among fish of the same genetic background. Hence, a stochastic variation in early development leads to a remarkably strong macroscopic phenotype. These fluctuations appear to be associated with maternal effects in the specification of the DFCs.

摘要

胚胎发育似乎进行得几乎完美精确。然而,目前还不清楚有多少潜在的微观可变性与正常发育兼容。在这里,我们通过研究斑马鱼内胚层中的细胞数量变化来量化脊椎动物发育中的胚胎间变异性。我们注意到,内胚层的一个亚群——背侧前体细胞(DFC,后来形成左右组织者)——的大小表现出比内胚层其余部分明显更多的胚胎间变异性。我们发现,在将胚胎孵育在高温下时,DFC 数量较少的胚胎中左右侧位缺陷的频率会急剧增加。此外,我们观察到,在相同遗传背景的鱼类中,这些波动具有很大的随机成分。因此,早期发育中的随机变化导致了非常明显的宏观表型。这些波动似乎与 DFC 特异性的母体效应有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/23a614f21f98/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/6dbdfe316599/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/674ef48ee9ca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/5cc3bc010264/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/23a614f21f98/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/6dbdfe316599/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/674ef48ee9ca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/5cc3bc010264/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4f4/7809618/23a614f21f98/gr3.jpg

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