Figure 1 As shown to the left side of Figure 1, Hydra, as a fresh water Cnidarian that is organized as a tubular organism with a gastric cavity. Morphologically it is structured with a head and tail pole. This involves a 1 head with a mouth hypostome and associated tentacles, 2 a body with outgrowing buds for asexual reproduction of the organism hydra also utilized sexual reproduction through egg and sperm fusion , and 3 a foot pole with its peduncle and basal disc.
The basal disc produces glycoproteins that allow the organism to attach to any substrate. The image to the right depicts the body wall structure of Hydra, with its ectoderm blue and endoderm yellow and its intervening extracellular matrix ECM composed of components reflective of modern day ECM e.
Laminins and collagens as well as many other ECM molecules. Hydra phylum Cnidaria and class Hydrozoa arose early during metazoan evolution approximately million years ago before the divergence of the protosomes and deuterostomes groups. Hydra is the first of existing organism with defined epithelial cell layers seen as a bilayer with junctional complexes present at the apical pole of the cells.
The epithelial cells of Hydra continuously turn over as seen in human skin epithelium. Hydra therefore has true epithelial tissues as compared to the more primitive groups such as the sponges. In this regard, sponges are thought to have diverged before Hydra. To appreciate the powerful extent of Hydra regenerative capacity it should be pointed out besides its ability to regenerate both its head and foot pole after excision of these poles from the body, Hydra also has the ability to regenerate its entire adult epithelial structure to include its ECM from pellets of cells obtained from non-enzymatically dissociated adult Hydra polyps.
Hydra also has interstitial cells that reside within the ectoderm and endoderm layers. These interstitial cells include 1, nematocytes the stinging cells from which Cnidaria derives its name 2 nerve cells, 3 and a number of other cell types to include i-cells that are stem cells from which the other interstitial cells continuously arise. It should be noted however, that the high regenerative capacity of Hydra is solely due to the epithelial cells because polyps lacking any i-cells are fully capable of complete body regeneration they are unable to feed themselves; however, because of the lack of nerve cells.
Hydra is pertinent to our understanding vertebrate regenerative mechanism because its molecular structural components cellular and ECM mimic those seen in higher vertebrates to include humans.
This review will discuss Hydra regeneration as a basis for our understanding of regenerative medicine in terms of its 1 cell-cell and cell-ECM interactions and its 2 molecular interactions based on current advances in genomic and transcriptome studies.
Gradient systems: Based on the pioneering studies by developmental biologists such as Lewis Wolpert and Hans Bode, we have a firm understanding of the basic tenants of gradient systems in Hydra. This occurs no matter where along the body one makes the incision. Based on grafting experiments, it was deduced that hydra polarity is dictated by a series of morphogenetic gradients that permit the head and basal disc to only form at specific locations along the longitudinal body axis.
Additional grafting experiments defined the existence of a head activator gradient highest at the hypostome and a basal activator gradient highest at the basal disc. Further studies defined 1 head activator gradient and 2 a head inhibitor gradient as well as a 3 basal disc activator gradient and 4 basal disc inhibitor gradient.
These inhibitor and activator gradients also provide instructions as to which end is apical and which end is basal. Therefore, when the head is removed, the head inhibitor is no longer is made, and this results in the head activator to induce a new head. Accordingly, the region with greatest amount of head activator will form a head structure; thereby restoring a gradient equilibrium from head to foot. More recent studies has shown that the epithelial cytoskeleton facilities the regenerative process.
As previously published by our laboratory, ECM formation is tightly coupled with the regenerative process as reviewed by Sarras. The epithelium acquires a flattened morphology due to the lack of an intervening ECM.
By three hours after the sealed epithelium bilayer forms, an up-regulation of ECM components occurs within the epithelial cells. By seven hours of this process, basal lamina components laminin and Col-TypeIV are translated and secreted between the epithelial bilayer and this is accompanied by the epithelial bilayer taking on its normal cellular morphology.
Following the appearance of the basal lamina, and twenty hours after decapitation was initiated, interstitial fibrillar collagens begin to be translated and appear between the two previously formed basal lamina layers adjacent to the basal extracellular border of the ectoderm and endoderm.
Once the interstitial matrix is formed, the ECM is now completely polymerized and a normal adult Hydra body wall structure is reformed. Normal head regeneration then is observed. These studies are reinforced by subsequent studies that show the same type of cell-ECM interactions occur when the ECM component blocking experiments are repeated using the hydra-cell-pellet system 11 where pellets are formed from dissociated hydra cells and these pellets then go on to form intact adult polyps.
The application of genomic and transcriptome studies has greatly advanced our understanding of the underlying molecular mechanisms of hydra regeneration 23 , 24 and this has implications to higher vertebrates and man. Additionally, single-cell RNA-seq for transriptonic analysis is emerging as a powerful tool to identify rare cell types and transient cell types that occur during regeneration.
For example, studies at UC at Davis have initiated studies from 25, single cells of Hydra and have been able to describe the differentiation pathways from the tree lineages of adult polyp. A combination of genomic and transriptonic studies indicate common molecular pathways shared by Cnidarians and higher vertebrates such as the 1 Wnt pathway, 2 RTK pathway with shared ligands such as FGF, 3 BMP pathway with the multiple Smads transcription factors , 4 TGF pathways, and 5 Notch pathway.
Additionally, epigenetic mechanisms are also functional in Hydra as seen in higher vertebrates and in human diseases such as Diabetes mellitus. From the early studies of Trembley in the s to current genomic and transcriptome studies, Hydra has provided a window into the underlying mechanisms of regeneration.
Based on 1 the shared "regenerative tool kit" of molecules observed among metazoans, 2 the simplified structure of Hydra, and 3 its high regenerative capacity; we have been able to elucidate regenerative mechanisms that can then be translated to and studied in higher vertebrates such as Homo sapiens.
Although much has been learned, it is apparent that we have learned only the most rudimentary aspects of a highly complicated process. The application of what we learn from Hydra will further our understanding of regeneration and allow us to apply these mechanisms to regenerative medicine which is the key to organ replacement and tissue repair.
The author wishes to express his appreciation to the National Institutes of Health, USA DK for funds that supported preparation and writing of this review. The author has no conflict of interests or commercial interests as related to the information provided in this review.
This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially. Withdrawal Guidlines. Publication Ethics.
Withdrawal Policies Publication Ethics. Mini Review Volume 7 Issue 1. Keywords: regenerative medicine, regeneration, Hydra. Cellular and mechanical processes pertaining to hydra regeneration Gradient systems: Based on the pioneering studies by developmental biologists such as Lewis Wolpert and Hans Bode, we have a firm understanding of the basic tenants of gradient systems in Hydra.
Trembley A. Ratcliff MJ. Abraham Trembley's strategy of generosity and the scope of celebrity in the mid-eighteenth century. Galliot B. Hydra, a fruitful model system for years.
Int J Dev Biol. Extracellular matrix mesoglea of Hydra vulgaris. Of note, for the computational aspect of the work on lineage trajectories, a collaboration with Jeffrey Farrell from Harvard University was crucial. Farrell, whom Juliano met at a developmental biology conference a few years ago, had developed an algorithm for finding cell trajectories based on following gene expression through the different stages of the zebrafish embryo.
For the Hydra application, they had to modify the algorithm to account for the absence of prior knowledge of the temporal sequence in gene expression. Importantly, although stem cells and their lineages are well studied in Hydra, the molecular underpinnings remained to be determined. She was particularly pleased that earlier work on cell trajectories from the s and s, which did not rely on the sophisticated tools available now, completely held up.
Since Juliano and her colleagues generated ATAC-seq data in addition to the Drop-seq data, they could also look into the regulatory relationships of genes that they thought were involved in the differentiation processes. With the modern tools, the team can go beyond this earlier work. Of particular interest to Juliano and her team is a previously unknown bipotential progenitor cell.
They discovered that neurons and gland cells might share a common progenitor state that is different from the progenitors for nematocytes. They hypothesize that a population of the neuron-gland progenitors is located in the ectoderm and generates neurons there.
Another population of these progenitor cells might cross over to the endoderm and gives rise to neurons or gland cells.
In the future, Juliano and her colleagues plans to follow up on this observation. In addition to the description of intermediate cell states, the single-cell sequencing approach also helped Juliano and her colleagues produce a molecular map of the nervous system.
The molecular information obtained will allow them to manipulate the nervous system to address these questions. Finally, Juliano also plans to manipulate signaling pathways or transcription factor expression and then to repeat the single-cell sequencing to see how these manipulations affect different lineage trajectories. Siebert, S. Stem cell differentiation trajectories in Hydra resolved at single-cell resolution. Science , Article Google Scholar. Download references. You can also search for this author in PubMed Google Scholar.
Correspondence to Nina Vogt. Reprints and Permissions. Vogt, N. Looking at Hydra cells one at a time. Nat Methods 16, Download citation. Published : 30 August Issue Date : September Anyone you share the following link with will be able to read this content:.
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