Elf3 deficiency during zebrafish development alters extracellular matrix organization and disrupts tissue morphogenesis.

Elf3 deficiency during zebrafish development alters extracellular matrix organization and disrupts tissue morphogenesis.
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DOI:
10.1371/journal.pone.0276255
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
Marrs, James A.
Marrs, James A.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sarmah, Swapnalee;Hawkins, Matthew R.;Manikandan, Priyadharshini;Farrell, Mark;Marrs, James A.

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E26转化特异性(ETS)家族转录因子在胚胎发生期间表达,并且参与各种细胞过程,例如细胞谱系的增殖、迁移、分化、血管生成、凋亡和存活,以确保适当的发育。在不同的癌症中检测到许多ETS家族成员的表达失调。人ELF 3是转录因子ETS家族的成员,在人类癌症的诱导和进展中起作用已被充分研究。然而,关于ELF 3在早期发育中的作用知之甚少。在此,我们克隆了斑马鱼elf 3基因,并分析了其在斑马鱼发育过程中的表达。斑马鱼elf 3是母体沉积的。在不同的发育阶段,elf 3在不同的组织中表达,主要是神经组织、内胚层来源的组织、软骨、心脏、原肾管、血管和脊索。在组织边界处表达水平较高。通过使用翻译阻断反义吗啉代寡核苷酸检查Elf 3功能丧失的后果,并使用CRISPR/Cas9敲低验证效果。Elf 3基因敲除产生了短而弯曲的幼虫,脊索,颅面软骨和鳍缺陷。鳍和脊索细胞外基质(ECM)结构紊乱。还观察到神经缺陷。视神经成束(捆绑)和树枝状的视顶盖是有缺陷的Elf 3-morphants,脊髓运动神经元的碎片是明显的。编码ECM蛋白和基质金属蛋白酶(MMP)的基因的失调和ECM的解体可能在观察到的Elf 3 morphants缺陷中发挥作用。我们的结论是,斑马鱼Elf 3所需的表皮,间充质和神经组织的发展。
E26 transformation specific (ETS) family transcription factors are expressed during embryogenesis and are involved in various cellular processes such as proliferation, migration, differentiation, angiogenesis, apoptosis, and survival of cellular lineages to ensure appropriate development. Dysregulated expression of many of the ETS family members is detected in different cancers. The human ELF3, a member of the ETS family of transcription factors, plays a role in the induction and progression of human cancers is well studied. However, little is known about the role of ELF3 in early development. Here, the zebrafish elf3 was cloned, and its expression was analyzed during zebrafish development. Zebrafish elf3 is maternally deposited. At different developmental stages, elf3 expression was detected in different tissue, mainly neural tissues, endoderm-derived tissues, cartilage, heart, pronephric duct, blood vessels, and notochord. The expression levels were high at the tissue boundaries. Elf3 loss-of-function consequences were examined by using translation blocking antisense morpholino oligonucleotides, and effects were validated using CRISPR/Cas9 knockdown. Elf3-knockdown produced short and bent larvae with notochord, craniofacial cartilage, and fin defects. The extracellular matrix (ECM) in the fin and notochord was disorganized. Neural defects were also observed. Optic nerve fasciculation (bundling) and arborization in the optic tectum were defective in Elf3-morphants, and fragmentation of spinal motor neurons were evident. Dysregulation of genes encoding ECM proteins and matrix metalloprotease (MMP) and disorganization of ECM may play a role in the observed defects in Elf3 morphants. We conclude that zebrafish Elf3 is required for epidermal, mesenchymal, and neural tissue development.
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