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XB-ART-58113
Development May 15, 2021; 148 (10):
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Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway.

Wang H , Wang C , Long Q , Zhang Y , Wang M , Liu J , Qi X , Cai D , Lu G , Sun J , Yao YG , Chan WY , Chan WY , Deng Y , Zhao H .


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.

PubMed ID: 33999995
Article link: Development


Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: cbl chrd.1 dab2 egr1 fermt2 fgf4 fgfr1 foxd3 mapk1 myc myod1 nedd4 nkx2-5 nodal3.1 odc1 pax3 plin1 pxn sia1 slc22a18 snai1 snai2 sox10 sox2 sox3 sox9 tbxt tfap2a twist1 wnt3a zic1
GO keywords: neural crest cell fate determination [+]
Antibodies: FLAG Ab3 Fgfr1 Ab4 Gapdh Ab3 Mapk 1/2 Ab12 Myc-tag Ab20 Pac-1 Ab1
Morpholinos: fermt2 MO2 fermt2 MO3
gRNAs referenced: fermt2 gRNA1

Phenotypes: Xla Wt + chd1 + animal cap explant (Fig.3.D) [+]

Article Images: [+] show captions