Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway

Author:

Wang Hui12,Wang Chengdong12,Long Qi12,Zhang Yuan12,Wang Meiling34,Liu Jie3,Qi Xufeng5,Cai Dongqing5,Lu Gang16,Sun Jianmin7,Yao Yong-Gang8910ORCID,Chan Wood Yee2,Chan Wai Yee1811,Deng Yi312ORCID,Zhao Hui1811ORCID

Affiliation:

1. Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China

2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

3. Department of Biology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, Gunadong 518055, China

4. School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150006, China

5. Key Laboratory of Regenerative Medicine of Ministry of Education, Department of Developmental and Regenerative Biology, Jinan University, Guangzhou, Guangdong 510632, China

6. CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

7. Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China

8. Kunming Institute of Zoology - The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Chinese Academy of Sciences, Kunming, Yunnan 650204, China

9. Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China

10. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China

11. Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China

12. Shenzhen Key Laboratory of Cell Microenvironment, Department of Chemistry, South University of Science and Technology of China, Shenzhen, Guangdong 518055, China

Abstract

ABSTRACT The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.

Funder

National Key R&D Program of China

National Key R&D Program of China, Synthetic Biology Research

Research Grants Council of Hong Kong

Chinese Academy of Sciences

Guangdong Natural Science Foundation

Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research

Key Research and Development Program of Ningxia Province

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Reference70 articles.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3