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BTB/POZ锌指蛋白Zbtb14对非洲爪蟾胚胎背腹和前后模式的协同调控

Coordinated regulation of the dorsal-ventral and anterior-posterior patterning of Xenopus embryos by the BTB/POZ zinc finger protein Zbtb14.

作者信息

Takebayashi-Suzuki Kimiko, Konishi Hidenori, Miyamoto Tatsuo, Nagata Tomoko, Uchida Misa, Suzuki Atsushi

机构信息

Amphibian Research Center, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan.

出版信息

Dev Growth Differ. 2018 Apr;60(3):158-173. doi: 10.1111/dgd.12431.

Abstract

During early vertebrate embryogenesis, bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family of growth factors play a central role in dorsal-ventral (DV) patterning of embryos, while other growth factors such as Wnt and fibroblast growth factor (FGF) family members regulate formation of the anterior-posterior (AP) axis. Although the establishment of body plan is thought to require coordinated formation of the DV and AP axes, the mechanistic details underlying this coordination are not well understood. Here, we show that a Xenopus homologue of zbtb14 plays an essential role in the regulation of both DV and AP patterning during early Xenopus development. We show that overexpression of Zbtb14 promotes neural induction and inhibits epidermal differentiation, thereby regulating DV patterning. In addition, Zbtb14 promotes the formation of posterior neural tissue and suppresses anterior neural development. Consistent with this, knock-down experiments show that Zbtb14 is required for neural development, especially for the formation of posterior neural tissues. Mechanistically, Zbtb14 reduces the levels of phosphorylated Smad1/5/8 to suppress BMP signaling and induces an accumulation of β-Catenin to promote Wnt signaling. Collectively, these results suggest that Zbtb14 plays a crucial role in the formation of DV and AP axes by regulating both the BMP and Wnt signaling pathways during early Xenopus embryogenesis.

摘要

在早期脊椎动物胚胎发育过程中,属于转化生长因子-β(TGF-β)家族的骨形态发生蛋白(BMPs)在胚胎背腹(DV)模式形成中起核心作用,而其他生长因子,如Wnt和成纤维细胞生长因子(FGF)家族成员则调节前后(AP)轴的形成。尽管人们认为身体模式的建立需要DV轴和AP轴的协调形成,但这种协调背后的机制细节尚不清楚。在这里,我们表明非洲爪蟾zbtb14的同源物在非洲爪蟾早期发育过程中对DV和AP模式的调节中起着至关重要的作用。我们表明,Zbtb14的过表达促进神经诱导并抑制表皮分化,从而调节DV模式。此外,Zbtb14促进后神经组织的形成并抑制前神经发育。与此一致,敲低实验表明Zbtb14是神经发育所必需的,特别是对于后神经组织的形成。从机制上讲,Zbtb14降低磷酸化Smad1/5/8的水平以抑制BMP信号,并诱导β-连环蛋白的积累以促进Wnt信号。总的来说,这些结果表明Zbtb14在非洲爪蟾早期胚胎发育过程中通过调节BMP和Wnt信号通路在DV和AP轴的形成中起关键作用。

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