HMGB factors are required for posterior digit development through integrating signaling pathway activities

Junji Itou, Noboru Taniguchi, Isao Oishi, Hiroko Kawakami, Martin Lotz, Yasuhiko Kawakami

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1151-1162
Number of pages12
JournalDevelopmental Dynamics
Volume240
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • BMP
  • HMGB
  • Limb
  • Posterior digit
  • Shh
  • Wnt

Fingerprint Dive into the research topics of 'HMGB factors are required for posterior digit development through integrating signaling pathway activities'. Together they form a unique fingerprint.

Cite this