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HMGB factors are required for posterior digit development through integrating signaling pathway activities
Author(s) -
Itou Junji,
Taniguchi Noboru,
Oishi Isao,
Kawakami Hiroko,
Lotz Martin,
Kawakami Yasuhiko
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22598
Subject(s) - biology , wnt signaling pathway , zebrafish , gastrulation , microbiology and biotechnology , gene knockdown , transcription factor , embryonic stem cell , chromatin , embryo , signal transduction , genetics , gene , embryogenesis
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.