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Involvement of Tsukushi in chick early embryogenesis

Tsukushi 参与鸡早期胚胎发生

基本信息

批准号：
17370082
负责人：
OHTA Kunimasa
金额：
$ 6.62万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17370082/
关键词：
Differentiation and Development Tsukushi BMP antagonist chick embryo 幹細胞網膜 Wnt signaling 再生医学

项目摘要

Wnt signaling orchestrates multiple aspects of central nervous system development, including cell proliferation and cell fate choices. In chick retina, Wnt2b is expressed in both the surface ectoderm and the retinal pigmented epithelium at optic cup stage. At later stage, Wnt2b is expressed in the margin almost tip of the embryonic chick retina. Using a clonal assay in retinal re-aggregation cultures, along with overexpression studies, it was proposed that Wnt2b plays a role in the maintenance and the proliferation of retinal progenitor cells without cell differentiation (Kubo, et. al., 2005).We have identified a BMP antagonist, Tsukushi (TSK), which is a soluble molecule containing 12 leucine-rich repeats and belongs to the Small Leucine-Rich Proteoglycan family. TSK is expressed in the primitive streak and Hensen's node during chick gastrulation and involved in their formation (Ohta, et. al., 2004 ; Ohta, et. al., 2006). TSK is also involved in the neural crest specification of Xenopus embryo by regulating BMP and Delta-1 activities at the boundary between the neural and the non-neural ectoderm (Kuriyama, et. al., 2006).When Wnt2b was over-expressed into chick optic vesicle at stage 10, Wnt2b induced prolonged proliferation of retinal progenitor cells in vitro. However, when Wnt2b was co-over-expressed with TSK, the proliferative activity of Wnt2b was almost inhibited. We now show that TSK, which is expressed in the ciliary marginal zone (CMZ) of chick retina, inhibits the retinal progenitor cells proliferation by functioning as Wnt signaling inhibitor.

WNT信号协调中枢神经系统发育的多个方面，包括细胞增殖和细胞命运选择。在雏鸡视网膜中，Wnt2b在视杯期的表面外胚层和视网膜色素上皮中均有表达。在胚胎后期，Wnt2b在胚胎视网膜的边缘几乎在顶端表达。利用视网膜再聚集培养中的克隆分析，结合过表达研究，提出Wnt2b在视网膜前体细胞的维持和增殖中发挥作用，而不是细胞分化(Kubo，et。我们已经鉴定出BMP拮抗剂Tsukushi(TSK)，它是一种含有12个富含亮氨酸重复序列的可溶性分子，属于富含亮氨酸的蛋白多糖小家族。TSK在雏鸡原肠发育过程中的原始条纹和Hensen‘s结节中表达，并参与它们的形成(Ohta，et.等人，2004年；Ohta等人。Al.，2006)。TSK还通过调节神经和非神经外胚层交界处的BMP和Delta-1活性，参与非洲爪哇胚胎的神经脊规范(栗山，et。当Wnt2b在第10阶段过表达到鸡视泡中时，Wnt2b在体外诱导了视网膜前体细胞的长时间增殖。而当Wnt2b与TSK共过表达时，Wnt2b的增殖活性几乎被抑制。我们现在发现，表达于鸡视网膜睫状缘(CMZ)的TSK通过抑制Wnt信号转导抑制视网膜前体细胞的增殖。