In most vertebrates, the notochord is a transient structure that provides axial support to the animal before the development of the vertebrae, when the notochord is subsequently remodelled into nuclei pulposi (NP) – components of the intervertebral disc. Mechanical forces and the extracellular matrix (ECM) are important for notochord formation and reorganisation. Now, Kathryn Cheah and colleagues investigate the role of β1 integrin (which interacts with the ECM) during notochord development. The authors develop a notochord-specific, β1 integrin knockout mouse line (Itgb1ΔND), which causes severe tail vertebrae malformations with missing or displaced NP. They traced these defects to loss of notochordal cells, fragmentation of the notochord and its positioning early in development, affecting the structure of the intervertebral disc. Using immunostaining and time-lapse imaging, the researchers show that during convergent extension, Itgb1ΔND cells lose directionality and migrate shorter distances. Moreover, embryos treated with anti-β1 integrin blocking antibodies exhibit planar cell polarity defects in the node. Finally, the authors show that cell-ECM interactions are also affected in β1 integrin-deficient cells, which adhere less well to ECM substrates in vitro. In sum, these data show that β1 integrin and cell-ECM adhesion is crucial during notochord morphogenesis, failure of which may contribute to human congenital spine malformations.
β1 integrin: integral in notochord development
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β1 integrin: integral in notochord development. Development 15 November 2020; 147 (22): e2202. doi:
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