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

Hui Wang1,2, Chengdong Wang1,2, Qi Long1,2

  • 1Key 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.

Development (Cambridge, England)
|May 17, 2021
PubMed

Insights

Kindlin2 is crucial for neural crest formation in Xenopus embryos, regulating the fibroblast growth factor (FGF) pathway independently of integrins. This finding offers new insights into early developmental processes.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Kindlin2 (Fermt2) is a focal adhesion protein vital for integrin activation and cell-adhesion.
  • Loss of Kindlin2 in mice causes early embryonic lethality, limiting studies on its developmental roles.
  • Neural crest (NC) cells are a transient population crucial for vertebrate development.

Purpose of the Study:

  • To investigate the role of Kindlin2 in neural crest (NC) formation in Xenopus embryos.
  • To elucidate the molecular mechanisms underlying Kindlin2's function in NC development.
  • To determine if Kindlin2's role in NC specification is dependent on integrin binding.

Main Methods:

  • Loss-of-function studies using morpholino antisense oligos (MOs) and CRISPR/Cas9 in Xenopus.
  • Analysis of NC formation and specification in treated embryos.
  • Rescue experiments using integrin-binding-deficient Kindlin2 mutants.
  • Investigation of the fibroblast growth factor (FGF) signaling pathway.

Main Results:

  • Kindlin2 is essential for Xenopus NC formation, with loss-of-function severely inhibiting NC specification.
  • Kindlin2's function in NC specification is independent of its integrin-binding ability.
  • Kindlin2 regulates the FGF signaling pathway by promoting the stability of FGF receptor 1.

Conclusions:

  • Kindlin2 plays a critical, previously unrecognized role in vertebrate NC development.
  • Kindlin2 regulates NC formation through modulation of the FGF signaling pathway, independent of integrin binding.
  • This study provides novel mechanistic insights into Kindlin2's function in developmental processes.
Keywords:
XenopusFGF receptorFGF signalKindlin2Neural crest

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