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

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.SFI Principle Investigator AwardDeposited by bulk impor

A polymorphic, thrombospondin domain-containing lectin is an oocyte marker in hydractinia: implications for germ cell specification and sex determination

We have identified a novel, multidomain, polymorphic lectin in the marine cnidarian Hydractinia echinata. The gene is expressed in oocytes and was therefore named CEL for cnidarian egg lectin. The predicted protein has an unusual domain architecture, consisting of variable numbers of thrombospondin type 1 domains, flanked by one N-terminal and two C-terminal galactose binding lectin domains. The diversity of the gene\u27s transcripts results from allelic polymorphism as well as alternative splicing. Hydractinia is dioecious and its sex has been reported previously to be genetically determined. We found intersexual colonies that were functional males, but had immature CEL-positive oocytes alongside mature sperm in the same gonads. Intersexuality was observed to be common in one population but not found in others. Hermaphroditic, self-fertile colonies were found in one locality; however, in these cases gonads contained either male or female gametes without mixed ones. Intersexuality that was considered to be a very rare event is apparently a more common phenomenon, at least in some populations. True hermaphroditism also occurs in this species. CEL can be considered as a marker for early oocyte differentiation and may play a role in germ cell specification and sex determination in cnidarians

An evolutionarily conserved soxb-hdac2 crosstalk regulates neurogenesis in a cnidarian

SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was coexpressed with SoxB2, and its downregulation phe-nocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other\u27s transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins