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Development April 28, 2021;
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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 .

The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin2 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 clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 techniques in Xenopus embryos severely inhibit the specification of 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 FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.

PubMed ID: 33912908
Article link: Development

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: dab2 egr1 fermt2 fgfr1 foxd3 gapdh myc myod1 nedd4 nkx2-5 pax3 snai1 snai2 sox9 tbxt tfap2a zic1
GO keywords: neural crest cell differentiation
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

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