A heat shock protein and Wnt signaling crosstalk during axial patterning and stem cell proliferation

Dev Biol. 2012 Feb 15;362(2):271-81. doi: 10.1016/j.ydbio.2011.11.014. Epub 2011 Dec 2.


Both Wnt signaling and heat shock proteins play important roles in development and disease. As such, they have been widely, though separately, studied. Here we show a link between a heat shock protein and Wnt signaling in a member of the basal phylum, Cnidaria. A heat shock at late gastrulation in the clonal marine hydrozoan, Hydractinia, interferes with axis development, specifically inhibiting head development, while aboral structures remain unaffected. The heat treatment upregulated Hsc71, a constitutive Hsp70 related gene, followed by a transient upregulation, and long-term downregulation, of Wnt signaling components. Downregulating Hsc71 by RNAi in heat-shocked animals rescued these defects, resulting in normal head development. Transgenic animals, ectopically expressing Hsc71, had similar developmental abnormalities as heat-shocked animals in terms of both morphology and Wnt3 expression. We also found that Hsc71 is upregulated in response to ectopic Wnt activation, but only in the context of stem cell proliferation and not in head development. Hsc71's normal expression is consistent with a conserved role in mitosis and apoptosis inhibition. Our results demonstrate a hitherto unknown crosstalk between heat shock proteins and Wnt/β-catenin signaling. This link likely has important implications in understanding normal development, congenital defects and cancer biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning / physiology*
  • Bromodeoxyuridine
  • Cell Proliferation
  • DNA Primers / genetics
  • Embryonic Stem Cells / physiology*
  • Gene Expression Regulation, Developmental / physiology
  • HSC70 Heat-Shock Proteins / genetics
  • HSC70 Heat-Shock Proteins / metabolism*
  • Hydrozoa / embryology*
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Molecular Sequence Data
  • RNA / genetics
  • RNA / isolation & purification
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Receptor Cross-Talk / physiology*
  • Sequence Analysis, DNA
  • Signal Transduction / physiology*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism


  • DNA Primers
  • HSC70 Heat-Shock Proteins
  • Wnt Proteins
  • beta Catenin
  • RNA
  • Bromodeoxyuridine

Associated data

  • GENBANK/JN400918