文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Ror2 增强原始生殖细胞的极性和定向迁移。

Ror2 enhances polarity and directional migration of primordial germ cells.

机构信息

Ob/Gyn Department, Center for Reproductive Sciences, University of California San Francisco, CA, USA.

出版信息

PLoS Genet. 2011 Dec;7(12):e1002428. doi: 10.1371/journal.pgen.1002428. Epub 2011 Dec 22.


DOI:10.1371/journal.pgen.1002428
PMID:22216013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3245308/
Abstract

The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC chemoattractant. We show that cultured PGCs undergo polarization, elongation, and reorientation in response to the chemotactic factor SCF (secreted KitL), whereas Ror2 PGCs are deficient in these SCF-induced responses. In the embryo, migratory PGCs exhibit a similar elongated geometry, whereas their counterparts in Ror2 mutants are round. The protein distribution of ROR2 within PGCs is asymmetric, both in vitro and in vivo; however, this asymmetry is lost in Ror2 mutants. Together these results indicate that Ror2 acts autonomously to permit the polarized response of PGCs to KitL. We propose a model by which Wnt5a potentiates PGC chemotaxis toward secreted KitL by redistribution of Ror2 within the cell.

摘要

原始生殖细胞 (PGC) 在多个胚胎结构中迁移到新生性腺,以确保通过配子将遗传信息传递给下一代,但我们对 PGC 迁移的机制的理解仍然不完整。在这里,我们确定了受体酪氨酸激酶样蛋白 Ror2 在 PGC 发育中的作用。在我们在遗传筛选中分离出的 Ror2 小鼠突变体中,PGC 的迁移和存活受到干扰,导致胚胎性腺中的 PGC 数量减少。Wnt5a 突变体中的类似表型表明 Wnt5a 作为配体在 PGC 中作用于 Ror2,尽管我们没有发现 WNT5A 作为 PGC 趋化因子的功能证据。我们表明,培养的 PGC 在响应趋化因子因子 SCF(分泌的 KitL)时会发生极化、伸长和重定向,而 Ror2 PGC 则缺乏这些 SCF 诱导的反应。在胚胎中,迁移的 PGC 表现出类似的伸长几何形状,而其在 Ror2 突变体中的对应物则是圆形的。ROR2 在 PGC 中的蛋白分布是不对称的,无论是在体外还是在体内;然而,这种不对称性在 Ror2 突变体中丢失。这些结果表明,Ror2 自主作用,允许 PGC 对 KitL 的极化反应。我们提出了一个模型,即 Wnt5a 通过在细胞内重新分配 Ror2 来增强 PGC 对分泌的 KitL 的趋化性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/20503122870a/pgen.1002428.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/8d6a906a4b3f/pgen.1002428.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/eaf9c889d1d3/pgen.1002428.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/a07c2fc200ac/pgen.1002428.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/173a15f35ada/pgen.1002428.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/70f3438d5913/pgen.1002428.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/35397f19a58e/pgen.1002428.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/20503122870a/pgen.1002428.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/8d6a906a4b3f/pgen.1002428.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/eaf9c889d1d3/pgen.1002428.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/a07c2fc200ac/pgen.1002428.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/173a15f35ada/pgen.1002428.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/70f3438d5913/pgen.1002428.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/35397f19a58e/pgen.1002428.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed69/3245308/20503122870a/pgen.1002428.g007.jpg

相似文献

[1]
Ror2 enhances polarity and directional migration of primordial germ cells.

PLoS Genet. 2011-12-22

[2]
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.

J Cell Biol. 2016-7-18

[3]
Novel domains of expression for orphan receptor tyrosine kinase Ror2 in the human and mouse reproductive system.

Dev Dyn. 2014-8

[4]
Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis.

Nat Med. 2012-2-19

[5]
Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A.

J Biol Chem. 2008-10-10

[6]
The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway.

Dis Model Mech. 2015-6

[7]
The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma.

Oncogene. 2009-10-5

[8]
Ror family receptor tyrosine kinases regulate the maintenance of neural progenitor cells in the developing neocortex.

J Cell Sci. 2012-2-10

[9]
Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation.

J Clin Invest. 2016-2

[10]
Insight into the role of Wnt5a-induced signaling in normal and cancer cells.

Int Rev Cell Mol Biol. 2015

引用本文的文献

[1]
The fantastic voyage: primordial germ cell migration through the developing mouse embryo.

Biochem Soc Trans. 2025-7-17

[2]
Beyond genes and environment: mapping biological stochasticity in aging.

Geroscience. 2025-4-29

[3]
Chicken Primordial Germ Cells Do Not Proliferate in Insulin-Lacking Media.

Int J Mol Sci. 2025-3-28

[4]
A tug-of-war between germ cell motility and intercellular bridges controls germline cyst formation in mice.

Curr Biol. 2024-12-16

[5]
Comprehensive profiling of migratory primordial germ cells reveals niche-specific differences in non-canonical Wnt and Nodal-Lefty signaling in anterior vs posterior migrants.

bioRxiv. 2024-8-30

[6]
Diaph1 knockout inhibits mouse primordial germ cell proliferation and affects gonadal development.

Reprod Biol Endocrinol. 2024-7-15

[7]
The journey of a generation: advances and promises in the study of primordial germ cell migration.

Development. 2024-4-1

[8]
Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway.

Curr Top Dev Biol. 2023

[9]
Histogenesis of intracranial germ cell tumors: primordial germ cell vs. embryonic stem cell.

Childs Nerv Syst. 2023-2

[10]
Celsr1 suppresses Wnt5a-mediated chemoattraction to prevent incorrect rostral migration of facial branchiomotor neurons.

Development. 2022-11-15

本文引用的文献

[1]
Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration.

PLoS One. 2011-10-6

[2]
Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice.

Biol Reprod. 2012-1-10

[3]
WNT5A/JNK and FGF/MAPK pathways regulate the cellular events shaping the vertebrate limb bud.

Curr Biol. 2010-11-4

[4]
The Golgi and the centrosome: building a functional partnership.

J Cell Biol. 2010-3-8

[5]
Ror2 is required for midgut elongation during mouse development.

Dev Dyn. 2010-3

[6]
Intestinal tube formation in Caenorhabditis elegans requires vang-1 and egl-15 signaling.

Dev Biol. 2009-12-11

[7]
Wnt5a regulates distinct signalling pathways by binding to Frizzled2.

EMBO J. 2009-11-12

[8]
The involvement of lethal giant larvae and Wnt signaling in bottle cell formation in Xenopus embryos.

Dev Biol. 2009-9-25

[9]
Ror2 receptor requires tyrosine kinase activity to mediate Wnt5A signaling.

J Biol Chem. 2009-10-30

[10]
Random versus directionally persistent cell migration.

Nat Rev Mol Cell Biol. 2009-8

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索