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

Wang，Hui1,2; Wang，Chengdong1,2; Long，Qi1,2; Zhang，Yuan1,2; Wang，Meiling3,4; Liu，Jie3; Qi，Xufeng5; Cai，Dongqing5; Lu，Gang1,6; Sun，Jianmin7; Yao，Yong Gang8,9,10; Chan，Wood Yee2; Chan，Wai Yee1,8,11; Deng，Yi3,12; Zhao，Hui1,8,11

2021-05-15

10.1242/dev.199441

Development (Cambridge, England)   影响因子和分区

1477-9129

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.

Xenopus FGF receptor FGF signal Kindlin2 Neural crest

SCI

英语

其他

WOS:000657670600014

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85106625580

Scopus

1.Key Laboratory for Regenerative Medicine,Ministry of Education,School of Biomedical Sciences,Faculty of Medicine,Chinese University of Hong Kong,China
2.School of Biomedical Sciences,Faculty of Medicine,Chinese University of Hong Kong,Hong Kong SAR,China
3.Department of Biology,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Shenzhen Key Laboratory of Cell Microenvironment,Southern University of Science and Technology,Shenzhen,China
4.School of Life Science and Technology,Harbin Institute of Technology,Harbin,150006,China
5.Key Laboratory of Regenerative Medicine of Ministry of Education,Department of Developmental and Regenerative Biology,Jinan University,Guangzhou,510632,China
6.CUHK-SDU Joint Laboratory on Reproductive Genetics,School of Biomedical Sciences,Faculty of Medicine,Chinese University of Hong Kong,Hong Kong SAR,China
7.Department of Pathogen Biology and Immunology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,1160 Shengli Street,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,650204,China
9.Key Laboratory of Animal Models and Human Disease Mechanisms,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,650223,China
10.Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming,650204,China
11.Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,Chinese University of Hong Kong,Hong Kong SAR,New Territories,China
12.Shenzhen Key Laboratory of Cell Microenvironment,Department of Chemistry,South University of Science and Technology of China,Shenzhen,518055,China

Wang，Hui,Wang，Chengdong,Long，Qi,et al. Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway[J]. Development (Cambridge, England),2021,148(10).

Wang，Hui.,Wang，Chengdong.,Long，Qi.,Zhang，Yuan.,Wang，Meiling.,...&Zhao，Hui.(2021).Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway.Development (Cambridge, England),148(10).

Wang，Hui,et al."Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway".Development (Cambridge, England) 148.10(2021).