PUBLICATION

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

Authors
Itou, J., Taniguchi, N., Oishi, I., Kawakami, H., Lotz, M., and Kawakami, Y.
ID
ZDB-PUB-110317-43
Date
2011
Source
Developmental dynamics : an official publication of the American Association of Anatomists   240(5): 1151-1162 (Journal)
Registered Authors
Kawakami, Yasuhiko
Keywords
HMGB, posterior digit, limb, Shh, Wnt, BMP
MeSH Terms
  • Animals
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism
  • Embryo, Mammalian/metabolism
  • Extremities/embryology*
  • Female
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology
  • HMGB Proteins/genetics
  • HMGB Proteins/metabolism*
  • HMGB1 Protein/genetics
  • HMGB1 Protein/metabolism
  • HMGB2 Protein/genetics
  • HMGB2 Protein/metabolism
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Pregnancy
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Zebrafish
PubMed
21384471 Full text @ Dev. Dyn.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping