Midgut Laterality Is Driven by Hyaluronan on the Right.

Developmental Cell
Aravind SivakumarNatasza A Kurpios

Abstract

For many years, biologists have focused on the role of Pitx2, expressed on the left side of developing embryos, in governing organ laterality. Here, we identify a different pathway during left-right asymmetry initiated by the right side of the embryo. Surprisingly, this conserved mechanism is orchestrated by the extracellular glycosaminoglycan, hyaluronan (HA) and is independent of Pitx2 on the left. Whereas HA is normally synthesized bilaterally as a simple polysaccharide, we show that covalent modification of HA by the enzyme Tsg6 on the right triggers distinct cell behavior necessary to drive the conserved midgut rotation and to pattern gut vasculature. HA disruption in chicken and Tsg6-/- mice results in failure to initiate midgut rotation and perturbs vascular development predisposing to midgut volvulus. Our study leads us to revise the current symmetry-breaking paradigm in vertebrates and demonstrates how enzymatic modification of HA matrices can execute the blueprint of organ laterality.

Citations

Feb 3, 2019·The Journal of Biological Chemistry·Vincent C Hascall
Jul 9, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Megan S LordJohn M Whitelock
Aug 14, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Hiroshi Hamada
Oct 14, 2020·Development·Julia GrzymkowskiNanette Nascone-Yoder
Nov 12, 2020·Biomolecules·Takashi KobayashiNaoki Itano
Feb 16, 2021·Macromolecules·Giulia GiubertoniHuib J Bakker
Feb 4, 2021·Genes·Paul W ChrystalAndrew J Waskiewicz
Aug 20, 2021·Communications Biology·Kevin G ByrnesJ Calvin Coffey

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