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  beta 1 Integrin regulates convergent extension in mouse notogenesis, ensures notochord integrity and the morphogenesis of vertebrae and intervertebral discs

Guo, S. S., Au, T. Y. K., Wynn, S., Aszodi, A., Chan, D., Fässler, R., et al. (2020). beta 1 Integrin regulates convergent extension in mouse notogenesis, ensures notochord integrity and the morphogenesis of vertebrae and intervertebral discs. Development, 147(22): dev192724. doi:10.1242/dev.192724.

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 Creators:
Guo, Shiny Shengzhen1, Author              
Au, Tiffany Y. K.2, Author
Wynn, Sarah2, Author
Aszodi, Attila2, Author
Chan, Danny2, Author
Fässler, Reinhard1, Author              
Cheah, Kathryn S. E.2, Author
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: PLANAR CELL-POLARITY; SONIC-HEDGEHOG; NUCLEUS PULPOSUS; FLOOR PLATE; NEURAL-TUBE; YOLK-SAC; GENE; NODE; EXPRESSION; FAMILYDevelopmental Biology; beta 1 integrin; Notochord; Convergent extension; Intervertebral discs; Hemi-vertebrae; Planar cell polarity;
 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 beta 1 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-beta 1 integrin blocking antibodies, to target node pit cells, disrupted asymmetric localization of VANGL2. Our study implicates pivotal roles of beta 1 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000596028000024
DOI: 10.1242/dev.192724
 Degree: -

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Title: Development
  Other : Development
Source Genre: Journal
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Publ. Info: Cambridge, Cambridgeshire : Company of Biologists
Pages: - Volume / Issue: 147 (22) Sequence Number: dev192724 Start / End Page: - Identifier: ISSN: 0950-1991
CoNE: https://pure.mpg.de/cone/journals/resource/954927546241