Junji Itou, Noboru Taniguchi, and Isao Oishi contributed equally to this work.
Special Issue Research Article
HMGB factors are required for posterior digit development through integrating signaling pathway activities
Article first published online: 7 MAR 2011
Copyright © 2011 Wiley-Liss, Inc.
Special Issue: Special Issue on Limb Development
Volume 240, Issue 5, pages 1151–1162, May 2011
How to Cite
Itou, J., Taniguchi, N., Oishi, I., Kawakami, H., Lotz, M. and Kawakami, Y. (2011), HMGB factors are required for posterior digit development through integrating signaling pathway activities. Dev. Dyn., 240: 1151–1162. doi: 10.1002/dvdy.22598
- Issue published online: 20 APR 2011
- Article first published online: 7 MAR 2011
- Manuscript Accepted: 4 FEB 2011
- Minnesota Medical Foundation
- National Institutes of Health
- Japan Society for the Promotion of Science
- posterior digit;
The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.5, Hmgb1−/−; Hmgb2+/− embryos exhibit a loss of digit5, the most posterior digit, in the forelimb. We show that Hmgb1−/−; Hmgb2+/− forelimbs have a reduced level of Shh signaling, as well as a clear downregulation of Wnt and BMP target genes in the posterior region. Moreover, we demonstrate that hmgb1 and hmgb2 in zebrafish embryos enhance Wnt signaling in a variety of tissues, and that double knockdown embryos have reduced Wnt signaling and shh expression in pectoral fin buds. Our data show that Hmgb1 and Hmgb2 function redundantly to enhance Wnt signaling in embryos, and further suggest that integrating Wnt, Shh, and BMP signaling regulates the development of digit5 in forelimbs. Developmental Dynamics 240:1151–1162, 2011. © 2011 Wiley-Liss, Inc.