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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Sivakumar A,Mahadevan A,Lauer ME,Narvaez RJ,Ramesh S,Demler CM,Souchet NR,Hascall VC,Midura RJ,Garantziotis S,Frank DB,Kimata K,Kurpios NAdoi
10.1016/j.devcel.2018.08.002subject
Has Abstractpub_date
2018-09-10 00:00:00pages
533-551.e5issue
5eissn
1534-5807issn
1878-1551pii
S1534-5807(18)30638-5journal_volume
46pub_type
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