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Glycobiology Advance Access published online on April 7, 2004
Glycobiology, doi:10.1093/glycob/cwh083
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Received January 17, 2004
Revised March 20, 2004
Accepted March 23, 2004

ORIGINAL ARTICLES

Role of heparan sulfate in dextral heart looping in chick

Xinping Yue 1, Thomas M. Schultheiss 2, Edward A. McKenzie 3, Robert D. Rosenberg 1*

1 Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2 Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
3 School of Biological Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester, M13 9PT, England

* To whom correspondence should be addressed. E-mail: rdrrosen{at}mit.edu.


  Abstract

Heparan sulfate (HS) has been shown to be involved in left-right asymmetry formation including the process of dextral heart looping during embryonic development. The structural features of HS required in this process, however, have not been explored. In this study, we examined the structure of HS from the heart forming regions (or heart fields) of Hamburger and Hamilton stage 5-9 chick embryos. No significant differences were found in HS to chondroitin sulfate ratio, HS chain length or [35S] sulfate incorporation at HS disaccharide level between the left and the right heart fields. Compared to other parts of the embryo, however, lower ratio of HS to chondroitin sulfate, shorter HS chain length and higher [35S] sulfate incorporation at 6-O position of the glucosamine residue in the HS chains were observed in the heart forming regions. Moreover, HS from the left and the right heart fields exhibit differential cleavage by heparanase, an endo-{beta}-D-glucuronidase that cleaves specific sequences within the HS chain. In embryo culture, microinjection of the active human heparanase enzyme into the right, but not the left pericardial cavity at stage 7-8+ resulted in reversed heart looping in a dose dependent manner. Heart reversal following microinjection of heparin or heparin derivatives suggests the involvement of N- and 6-O-sulfation, but not 2-O-sulfation in the heart looping process.

Key words: 6-O-sulfation, chick, heart looping, heparan sulfate, heparanase


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[Abstract] [Full Text] [PDF]


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