title: A heat shock protein and Wnt signaling crosstalk during axial patterning and stem cell proliferation.
abstract: 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.
authors.affiliation: School of Natural Sciences and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Duffy
authors.forename: R Cathriona
authors.initials: RC
authors.lastname: Millane
authors.forename: Uri
authors.initials: U
authors.lastname: Frank
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D037402:Hydrozoa / Q000196:embryology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000502:physiology*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017931:DNA Primers; D050883:HSC70 Heat-Shock Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D012313:RNA; D001973:Bromodeoxyuridine