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

Abstract

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.

Regulation and plasticity of intestinal stem cells during homeostasis and regeneration

“…A model that directly links injury to regenerative signals was described in the freshwater polyp Hydra. Here, cells undergoing apoptosis secrete Wnt3 to promote cell division of neighboring cells (Galliot, 2013). In vitro models such as organoids represent simple systems that may help to dissect signals that restore homeostasis after injury (Huch and Koo, 2015;Clevers, 2016).…”

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy

“…Wnt3 is a member of the Wnt family of signaling proteins whose activation has been implicated in oncogenesis in addition to regulating a number of developmental processes. This secreted Wnt3 activates the β-catenin pathway in surrounding cells, which leads to an increased rate of proliferation [31–33]. The importance of compensatory proliferation in head regeneration is demonstrated when blocking apoptosis through use of a caspase inhibitor prevents head regeneration from occurring.…”

How to use Hydra as a model system to teach biology in the classroom

“…(Bode, 2012;Shimizu, 2012). Head regeneration is well documented from Trembley's original experiment to the modern synthesis of the cellular and molecular events that drive the process (Holstein et al, 2003;Galliot and Chera, 2010). In essence it involves the transformation of a piece of gastric tissue into an organizer that recruits stem cells and progenitors to rebuild the missing structure (see next section, and also reviews by Bode and by Shimizu in this issue).…”