• Home
  • Search Results
  • β1 Integrin regulates convergent extension in mouse notogenesis, ensures notochord integrity and the morphogenesis of vertebrae and intervertebral discs.

β1 Integrin regulates convergent extension in mouse notogenesis, ensures notochord integrity and the morphogenesis of vertebrae and intervertebral discs.

Development (Cambridge, England) (2020-10-15)
Shiny Shengzhen Guo, Tiffany Y K Au, Sarah Wynn, Attila Aszodi, Danny Chan, Reinhard Fässler, Kathryn S E Cheah
ABSTRACT

The notochord drives longitudinal growth of the body axis by convergent extension, a highly conserved developmental process that depends on non-canonical Wnt/planar cell polarity (PCP) signaling. However, the role of cell-matrix interactions mediated by integrins in the development of the notochord is unclear. We developed transgenic Cre mice, in which the β1 integrin gene (Itgb1) is ablated at E8.0 in the notochord only or in the notochord and tail bud. These Itgb1 conditional mutants display misaligned, malformed vertebral bodies, hemi-vertebrae and truncated tails. From early somite stages, the notochord was interrupted and displaced in these mutants. Convergent extension of the notochord was impaired with defective cell movement. Treatment of E7.25 wild-type embryos with anti-β1 integrin blocking antibodies, to target node pit cells, disrupted asymmetric localization of VANGL2. Our study implicates pivotal roles of β1 integrin for the establishment of PCP and convergent extension of the developing notochord, its structural integrity and positioning, thereby ensuring development of the nucleus pulposus and the proper alignment of vertebral bodies and intervertebral discs. Failure of this control may contribute to human congenital spine malformations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fibronectin bovine plasma, solution, sterile-filtered, BioReagent, suitable for cell culture
Roche
Anti-Digoxigenin-AP, Fab fragments, from sheep
Sigma-Aldrich
Sodium orthovanadate, ≥90% (titration)
Sigma-Aldrich
Anti-Laminin antibody produced in rabbit, 0.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Vinculin antibody produced in mouse, clone hVIN-1, ascites fluid
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-Sox9 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-GAPDH Mouse mAb (6C5), liquid, clone 6C5, Calbiochem®
Sigma-Aldrich
Anti-Integrin β1 Antibody, clone MB1.2, clone MB1.2, Chemicon®, from rat
Sigma-Aldrich
Anti-Fibronectin Antibody, Chemicon®, from rabbit