Autoregulatory and repressive inputs localize
            <i>Hydra Wnt3</i>
            to the head organizer

Nakamura, Yukio; Tsiairis, Charisios D.; Özbek, Suat; Holstein, Thomas W.

doi:10.1073/pnas.1018109108

Cited by 123 publications

(202 citation statements)

References 45 publications

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“…In line with these new hypotheses, we found that Wnt signaling can also be effectively suppressed at the transcriptional level (Nakamura et al 2011). The removal of a repressor element in the regulatory region of Wnt3 resulted in an expansion of the Wnt3 gene expression domain toward the gastric region (Fig.…”

Section: Local Restriction Of the Organizersupporting

confidence: 60%

“…These two Wnt clusters are also supported by recent molecular phylogenies on Wnt genes (Cho et al 2010;Janssen et al 2010). How the interacting Wnt ligands are regulated is rather unknown so far, but it is tempting to speculate that there is a regulative hierarchy of Wnt gene expression similar to that described for Hydra (Nakamura et al 2011) or Drosophila (van de Wetering et al 1997Lessing and Nusse 1998).…”

Section: Synteny and Evolution Of Wnt Genesmentioning

confidence: 65%

“…Activation of Wnt signaling stimulates the expression of all Wnt genes as well as of the Wnt target genes Tcf and Brachyury, resulting in numerous spot-like Wnt expression domains along the body column (Broun et al 2005;Guder et al 2006b;Nakamura et al 2011). It is generally accepted that each of these Wnt signaling centers creates a gradient of diffusible Wnt, although thus far the distribution of none of the cnidarian Wnts has been visualized by using either antibodies or reporter constructs.…”

Section: Short-and Long-range Wnt Signalingmentioning

confidence: 99%

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The Evolution of the Wnt Pathway

Holstein

2012

Cold Spring Harbor Perspectives in Biology

190

176

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Wnt genes are important regulators of embryogenesis and cell differentiation in vertebrates and insects. New data revealed by comparative genomics have now shown that members of the Wnt signaling pathway can be found in all clades of metazoans, but not in fungi, plants, or unicellular eukaryotes. This article focuses on new data from recent genomic analyses of several basal metazoan organisms, providing evidence that the Wnt pathway was a primordial signaling pathway during evolution. The formation of a Wnt signaling center at the site of gastrulation was instrumental for the formation of a primary, anterior-posterior body axis, which can be traced throughout animal evolution.

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Section: Local Restriction Of the Organizersupporting

confidence: 60%

Section: Synteny and Evolution Of Wnt Genesmentioning

confidence: 65%

Section: Short-and Long-range Wnt Signalingmentioning

confidence: 99%

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The Evolution of the Wnt Pathway

Holstein

2012

Cold Spring Harbor Perspectives in Biology

190

176

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“…As a result of caspase activation, signaling molecules as Wnt3 are transiently release leading to the activation of β-catenin signaling in the surrounding cycling progenitors followed by their mitotic division (not depicted here, see in (Chera et al 2009b;Galliot and Chera 2010). A couple of hours after bisection a series of early genes are upregulated in the endodermal epithelial cells, including the Wnt3 gene that contains CREs in its regulatory sequences (Gauchat et al 1998;Technau and Bode 1999;Hobmayer et al 2000;Kaloulis et al 2004;Chera et al 2007;Chera et al 2009b;Chera et al 2011;Lengfeld et al 2009;Nakamura et al 2011). By contrast after decapitation (80% body length) head injuryinduced apoptosis and apoptosis-induced compensatory proliferation are not observed (Galliot and Chera 2010) and Wnt3 seems to be directly upregulated in the epithelial cells (Lengfeld et al 2009).…”

Section: % Inhibited After Decapitationmentioning

confidence: 99%

“…Similarly RSK, CREB and CBP require a functional pathway to maintain their level of expression and their head-regeneraiton specific upregulation (Chera et al 2011). The recent functional dissection of the regulatory sequences of Wnt3 identified an autoregulatory element as well as a repressor element that restricts Wnt3 expression to the organizer region but also binding sites for CREB (Nakamura et al 2011). Therefore, beside their participation in injury-induced apoptosis in the interstitial cells, RSK, CREB and CBP also likely play in the epithelial cells a key role to modulate the expression of the early head regeneration genes that are essential for the establishment of the head organizer ( Figure 5).…”

Section: Early Genes In the Head Organizer And Putative Regulation Bymentioning

confidence: 99%

Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra

Galliot

2012

Dev Genes Evol

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The freshwater Hydra polyp provides a unique model system to decipher the mechanisms underlying adult regeneration. Indeed a single cut initiates two distinct regenerative processes, foot regeneration on one side, head regeneration on the other side, the latter relying on the rapid formation of a local head organizer. Two aspects are discussed here, the asymmetric cellular remodeling induced by mid-gastric bisection and the signaling events that trigger head organizer formation. In head-regenerating tips (but not in foot ones) a wave of cell death takes place immediately, leading the apoptotic cells to transiently release Wnt3 and activate the β-catenin pathway in the neighboring cycling cells to push them through mitosis. This process, which mimics the apoptosis-induced compensatory proliferation process deciphered in Drosophila larvae regenerating their discs likely corresponds to an evolutionarily-conserved mechanism, also at work in Xenopus tadpoles regenerating their tale or mice regenerating their skin or liver. How is this process generated in Hydra? Several studies pointed to the necessary activation of the ERK 1-2 and MAPK pathways during early head regeneration and indeed ERK 1-2 inhibition or RSK, CREB, CBP knockdown prevent injury-induced apoptosis and head regeneration. The current scenario involves an asymmetric activation of the MAPK/CREB pathway to trigger injury-induced apoptosis in the interstitial cells, and, in the epithelial cells a CREB/CBP-dependent transcriptional activation of early genes essential for head organizing activity as wnt3, HyBra1, prdl-a. The question now is how bisection in the rather uniform central region of the polyp can generate this immediately asymmetric signaling.

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Regeneration inHydra

Galliot

2013

Encyclopedia of Life Sciences

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Hydra freshwater polyps have a remarkable ability to regenerate after bisection or even after dissociation, and thus offer a unique model system to investigate the cellular and molecular basis of eumetazoan regeneration. From a single cut along the body column two different types of regeneration arise: foot regeneration from the apical part and head regeneration from the basal part. The high proportion of stem cells in the Hydra body column supports these fast and efficient processes. Grafting experiments proved that the gastric tissue in the head‐regenerating tip rapidly develops a de novo organising activity, as evidenced by the induction of an ectopic axis when transplanted onto a host. The molecular mechanisms involved in this transformation rely on the immediate activation of the mitogen activated protein kinase (MAPK) pathway and the subsequent activation of the canonical Wnt3 pathway. This early phase is followed by a patterning phase, when head regeneration requires de novo neurogenesis. Key Concepts: Hydra is a bilayered freshwater solitary polyp that belongs to Cnidaria, a phylum that also includes jellyfish, sea anemones and corals. Cnidaria as sister group to bilaterians, belongs to Eumetazoa, that is, all animals that have a differentiated gut and nervous system. Hydra tissues contain three distinct stem cell populations that continuously cycle but cannot replace each other. The ectodermal and endodermal myoepithelial cells are differentiated cells that are also unipotent stem cells. These cells that cycle rather slowly provide all epithelial cells; however, these two lineages cannot replace each other. By contrast, the third lineage is multipotent, that is, the interstitial stem cells that cycle much faster (every 24–30 h) and provide nerve cells, nematocytes, gland cells as well as germinal cells. Head regeneration requires a complex 3D reconstruction when foot regeneration appears much simpler, similar to tissue repair. Head regeneration relies on a head organising activity that develops in several hours after bisection from the gastric tissue in the regenerating tip. This activity can be quantified at every time point of the regenerative process by lateral transplantation. Successive waves of gene and protein regulations characterise each phase of head regeneration: immediate, early, early‐late and late. The immediate activation of the MAPK/RSK/CREB pathway followed by the early activation of the Wnt3 pathway participates in the establishment of the head organising activity. After midgastric bisection, activation of the MAPK pathway leads to injury‐induced apoptosis of the interstitial cells, a cellular event that initiates head regeneration by activating the Wnt3 pathway in interstitial progenitors and subsequently in endodermal epithelial cells. Head regeneration in Hydra is highly plastic, as it is maintained, although at a slower pace, when cell cycling is transiently inhibited or slowed down in the early phase of head regeneration. This suggests that cell proliferation is not essential for Hydra regeneration, at least during the early phase, a condition named morphallaxis. Interstitial cycling cells play an important role at the early phase of head regeneration: those located at the tip receive signals from the apoptotic cells and rapidly divide, whereas those located more distantly migrate towards the wound. Both processes lead to the formation of a dense zone of progenitors in the regenerating tip. Head regeneration in Hydra is highly plastic, as it is maintained after elimination of the interstitial cell lineage, indicating that epithelial cells alone can drive the head regeneration process efficiently although with a significant delay. Since 2002, transgenic strategies were successfully developed in Hydra , allowing first the transient expression of reporter constructs, and since 2006 the establishment of stable transgenic lines.

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Autoregulatory and repressive inputs localize Hydra Wnt3 to the head organizer

Cited by 123 publications

References 45 publications

The Evolution of the Wnt Pathway

The Evolution of the Wnt Pathway

Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra

Regeneration inHydra

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