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- Title
Versican/PG-M is essential for ventricular septal formation subsequent to cardiac atrioventricular cushion development.
- Authors
Hatano, Sonoko; Kimata, Koji; Hiraiwa, Noriko; Kusakabe, Moriaki; Isogai, Zenzo; Adachi, Eijiro; Shinomura, Tamayuki; Watanabe, Hideto
- Abstract
Versican (Vcan)/proteoglycan (PG)-M is a large chondroitin sulfate proteoglycan which forms a proteoglycan/hyaluronan (HA) aggregate in the extracellular matrix (ECM). We tried to generate the Vcan knockout mice by a conventional method, which resulted in mutant mice VcanΔ3/Δ3 whose Vcan lacks the A subdomain of the G1 domain. The Vcan knockout embryos died during the early development stage due to heart defects, but some VcanΔ3/Δ3 embryos survived through to the neonatal period. The hearts in VcanΔ3/Δ3 newborn mice showed normal cardiac looping, but had ventricular septal defects. Their atrioventricular canal (AVC) cushion was much smaller than those of wild-type (WT) embryos, and the extracellular space for cardiac jelly was narrow. The Vcan deposition in the VcanΔ3/Δ3 AVC cushion had decreased, whereas the HA deposition was maintained and condensed. In the tip of ventricular septa, both Vcan and HA had decreased. The cell proliferation based on the number of Ki67-positive cells had remarkably increased in both the AVC cushion and ventricular septa, compared with that of WT embryos. VcanΔ3/Δ3 seemed to have endocardial and mesenchymal mixed characteristics. When the ex vivo explant culture of these regions was performed on the collagen gel, hardly any migration to make sufficient space for the ECM construction was apparent. Our results suggest that the proteoglycan aggregates are necessary in both the AVC cushion and ventricular septa to fuse interventricular septa, and the Vcan A subdomain plays an essential role for the interventricular septal formation by constituting the proteoglycan aggregates.
- Subjects
VERSICAN; VENTRICULAR septal defects; PROTEOGLYCANS; HYALURONIC acid; EXTRACELLULAR matrix; ENDOCARDIAL cushion defects; CELL proliferation
- Publication
Glycobiology, 2012, Vol 22, Issue 9, p1268
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cws095