Malevolent Designer - How Creationism's Intelligent [Sic] Designer' Denied Us The Ability To Regenerate Limbs But Gave It To A Jellyfish

The jellyfish Cladonema pacificum exhibits branched tentacles that can robustly regenerate after amputation.

© 2023 Sosuke Fujita, The University of Tokyo

Cladonema pacificum

How jellyfish regenerate functional tentacles in days | The University of Tokyo.

Imagine for a moment that you're creationism's putative intelligent [sic] designer (the one on whom they've bestowed all the 'omnis' like omnipotence, omniscience and omnibenevolence) and you've created lots of creatures with the ability to regenerate body parts like limbs, tails and tentacles when they lose them, but you haven't given this ability to all of your creation, especially the one you supposedly love above all the others because its designed to be in your own image and you created all the other species to be at the disposal of your favourite.

What are some of the reasons you might have created them without the ability to regenerate missing body parts?

• Incompetence? It can't be that because you're omnipotent, so nothing is impossible for you.
• Amnesia? You just forgot to! It can't be that because you're omniscient, so know all things, past present and future so must remember creating the ability to regenerate limbs in salamanders, for example.
• If it wasn't incompetence and it wasn't amnesia, it must have been deliberate. You chose not to because you didn't want your special creation to have this ability - even though you're allegedly omnibenevolent.

So creationists must be mistaken in at least one and possibly all of the qualities they've bestowed on you.

Or you've chosen to create humans and other animals, especially mammals, birds and most reptiles, less perfectly than you could have created them because you prefer to see them suffer when they have accidents.

And yet, according to recently published research by a Japanese research team, you gave that ability to a small jellyfish so it can regenerate its tentacles. Unless you prefer to see a human amputee struggle but not a jellyfish, why would you do that?

I'll leave that question for creationists to perform their usual intellectual gymnastic over, so they can continue to feel like the special creation of an omnipotent creator of the universe who loves them above the rest of its creation that it created just for them, like a narcissistic toddler, who thinks the world is just for him/her and someone must be making sure it stays that way.

The problem with regeneration is a result of the phenomenon that, better than almost anything else, shows the lack of intelligent design in all multicellular organisms - epigenetics. The whole complex system of epigenetics is needed to overcome the problem that the cells of a multicellular organism replicated using exactly the same method as a single-celled organism, so the entire genome is reproduced in every cell. But the benefit of multicellularity is in cell specialisation, using just a few of the genes in the genome, so all the unneeded genes need to be switched off.

As the embryo develops and differentiates each cell type gives rise to different cell lines, each with epigenetic settings that are inherited by daughter cells, so that the tissues a limb is made from - bone, muscles, nerves, tendons, blood vessels, skin, etc. are each made from different cells that are themselves descended from different stem cells in a family tree of epigenetic settings that go right back to the initial zygote.

This means that every new zygote that is the result of the fusion of two specialised cells (sperm and ovum) has to have its epigenetic setting reset so it can give rise to any of the specialised cells in the eventual adult. Every one of your several trillion cells has your entire genome in its nucleus, replicated every time a cell divides, complete with the risk of mistakes that give rise to cancer.

And all this could have been avoided if the cells of multicellular organisms replicated in such a way that the daughter cells had just the genes they need, no more and no less. That should not have been beyond the wit of an omnipotent designer who can create living things out of dust. Instead, we have the unnecessary complexity that characterises evolved systems and distinguishes them from intelligently designed systems.

And this also means that you can't simply grow a new limb from, say, bone cells, muscle cells, nerve or skin cells. What you would need is a stem cell from which all the tissues in a limb are made and a method of organising them into the organised functional structure of a limb.

And yet none of that should be impossible for an omnipotent creator god, especially one who has already designed a method for doing it in amphibians such as the axolotl, for example.

So how is this achieved in a jellyfish? The press release from the University of Tokyo explains the team's research:

At about the size of a pinkie nail, the jellyfish species Cladonema can regenerate an amputated tentacle in two to three days — but how? Regenerating functional tissue across species, including salamanders and insects, relies on the ability to form a blastema, a clump of undifferentiated cells that can repair damage and grow into the missing appendage. Jellyfish, along with other cnidarians such as corals and sea anemones, exhibit high regeneration abilities, but how they form the critical blastema has remained a mystery until now.

A research team based in Japan has revealed that stem-like proliferative cells — which are actively growing and dividing but not yet differentiating into specific cell types — appear at the site of injury and help form the blastema.

The findings were published in the scientific journal PLOS Biology.

“Importantly, these stem-like proliferative cells in blastema are different from the resident stem cells localized in the tentacle,” said corresponding author Yuichiro Nakajima, lecturer in the Graduate School of Pharmaceutical Sciences at the University of Tokyo. “Repair-specific proliferative cells mainly contribute to the epithelium — the thin outer layer — of the newly formed tentacle.”

Two stem-like cell populations in the regenerating tentacle
Resident stem cells (green) and repair-specific proliferative cells (red) contribute to tentacle regeneration in Cladonema.

©2023 Sosuke Fujita, The University of Tokyo

The resident stem cells that exist in and near the tentacle are responsible for generating all cellular lineages during homeostasis and regeneration, meaning they maintain and repair whatever cells are needed during the jellyfish’s lifetime, according to Nakajima. Repair-specific proliferative cells only appear at the time of injury.

“Together, resident stem cells and repair-specific proliferative cells allow rapid regeneration of the functional tentacle within a few days,” Nakajima said, noting that jellyfish use their tentacles to hunt and feed.

This finding informs how researchers understand how blastema formation differs among different animal groups, according to first author Sosuke Fujita, a postdoctoral researcher in the same lab as Nakajima in the Graduate School of Pharmaceutical Sciences.

“In this study, our aim was to address the mechanism of blastema formation, using the tentacle of cnidarian jellyfish Cladonema as a regenerative model in non-bilaterians, or animals that do not form bilaterally — or left-right — during embryonic development,” Fujita said, explaining that the work may provide insight from an evolutionary perspective.

Regeneration of the jellyfish tentacle
At 72 hours after amputation, the regenerating tentacle of Cladonema is fully functional.

© 2023 Sosuke Fujita, The University of Tokyo

Salamanders, for example, are bilaterian animals capable of regenerating limbs. Their limbs contain stem cells restricted to specific cell-type needs, a process that appears to operate similarly to the repair-specific proliferative cells observed in the jellyfish.

“Given that repair-specific proliferative cells are analogues to the restricted stem cells in bilaterian salamander limbs, we can surmise that blastema formation by repair-specific proliferative cells is a common feature independently acquired for complex organ and appendage regeneration during animal evolution,” Fujita said.

The cellular origins of the repair-specific proliferative cells observed in the blastema remain unclear, though, and the researchers say the currently available tools to investigate the origins are too limited to elucidate the source of those cells or to identify other, different stem-like cells.

“It would be essential to introduce genetic tools that allow the tracing of specific cell lineages and the manipulation in Cladonema,” Nakajima said. “Ultimately, understanding blastema formation mechanisms in regenerative animals, including jellyfish, may help us identify cellular and molecular components that improve our own regenerative abilities.”

Technical details and background to the subject are given in the Abstract and Introduction to the team's paper in PLOS Biology

Abstract

Blastema formation is a crucial process that provides a cellular source for regenerating tissues and organs. While bilaterians have diversified blastema formation methods, its mechanisms in non-bilaterians remain poorly understood. Cnidarian jellyfish, or medusae, represent early-branching metazoans that exhibit complex morphology and possess defined appendage structures highlighted by tentacles with stinging cells (nematocytes). Here, we investigate the mechanisms of tentacle regeneration, using the hydrozoan jellyfish Cladonema pacificum. We show that proliferative cells accumulate at the tentacle amputation site and form a blastema composed of cells with stem cell morphology. Nucleoside pulse-chase experiments indicate that most repair-specific proliferative cells (RSPCs) in the blastema are distinct from resident stem cells. We further demonstrate that resident stem cells control nematogenesis and tentacle elongation during both homeostasis and regeneration as homeostatic stem cells, while RSPCs preferentially differentiate into epithelial cells in the newly formed tentacle, analogous to lineage-restricted stem/progenitor cells observed in salamander limbs. Taken together, our findings propose a regeneration mechanism that utilizes both resident homeostatic stem cells (RHSCs) and RSPCs, which in conjunction efficiently enable functional appendage regeneration, and provide novel insight into the diversification of blastema formation across animal evolution.

Introduction

Regeneration, the phenomenon of re-forming missing body parts, is widespread among metazoans. Common regenerative processes include wound closure immediately after injury; formation of the cellular source, or blastema, that reconstitutes the lost tissue; and regrowth of the tissue that integrates different cellular behaviors such as proliferation and differentiation [1]. Among these regenerative responses, blastema formation is a critical step that can distinguish regenerative and non-regenerative systems. Indeed, most mammalian and avian species do not form blastema upon injury while wound closure occurs normally [2]. Understanding blastema formation mechanisms in highly regenerative animals may therefore help us identify the necessary elements to potentially improve our regenerative abilities.

Blastema can be defined as an undifferentiated cellular mass that contains cells with mitotic capacity and appears after damage such as amputation [3,4]. Accumulating evidence has suggested that methods of blastema formation vary among animals with high regenerative abilities [5]. For example, in planarians, pluripotent stem cells called neoblasts that are distributed throughout the body are recruited to the injury site to produce blastema [6]. Salamanders can regenerate adult limbs upon amputation via blastema formation, but the underlying cellular mechanisms vary among species: in the axolotl, tissue-specific stem cells contribute to blastema, while in the newt, muscle fibers dedifferentiate into proliferative progenitor cells to behave as blastema [7]. During zebrafish caudal fin regeneration, both osteoblast-derived dedifferentiated cells and resident progenitor cells migrate to the wound site to form blastema [8,9]. These studies support the idea that the supply of blastema has diversified across the animal kingdom, whose members utilize resident stem/progenitor cells and/or repair-specific de novo proliferative cells to reconstruct lost body parts. While mechanisms of blastema formation have been studied extensively in a limited number of regenerative animals, little is known about their evolutionary characteristics: Which elements are acquired as lineage-specific novelties and which are widely conserved within highly regenerative species? In particular, the current understanding of blastema formation largely relies on bilaterian models, and thus the mechanisms of blastema formation outside of bilaterians remain poorly understood.

Among various regeneration contexts, appendage regeneration is widely observed in bilaterians (e.g., amphibian limbs and fish fins) and is suitable for understanding the evolution of regenerative processes [3,10]. The bilaterian program of blastema formation during appendage regeneration is associated with repair-specific stem/progenitor cells [7,9,11]. Yet, to elucidate the evolutionary history of blastema formation programs, their mechanisms must be studied in early-branching metazoans in addition to bilaterian models.

Cnidarians (corals, sea anemones, hydroids, and jellyfish) are among the earliest branching metazoans, composed of 2 major groups Anthozoa and Medusozoa, forming a diverse phylum that contains over 10,000 species, and stand at a unique phylogenetic position as the sister group to bilaterians (Fig 1A). While cnidarians display considerably divergent morphologies and life cycles, represented by the polyp and medusa stages; their common traits are a diploblastic radially symmetric body along with tentacles as the well-defined appendages that bear the stinging cells, nematocytes (cnidocytes) [12,13]. Although regenerative potential may vary among the group, most documented cnidarian species are capable of regenerating lost tissues and organs, and some can even regenerate their entire body [14,15].

Fig 1. Regeneration processes and potentials of the Cladonema medusa tentacle.

(A) The phylogenetic tree of Bilateria and Cnidaria, composed of Anthozoa and Medusozoa. (B) Medusa of Cladonema pacificum. U: umbrella, M: manubrium, Ra: radial canal, Ri: ring canal, T: tentacle. (C) Tentacle of Cladonema medusa. O: ocellus, TB: tentacle bulb, Br: branch, NC: nematocyte cluster. (D) Tentacle regeneration processes after amputation while retaining the bulb. hpa: hour post-amputation. Yellow arrows indicate nematocyte clusters. n = 234/236 (tentacles). (E) Scheme of the tentacle regeneration that retains the bulb. (F) Distribution of mature nematocytes and localization of muscle fibers during tentacle regeneration. DAPI for poly-γ-glutamate (green) and nuclei (blue), and Phalloidin for F-actin (red). Yellow arrows indicate nematocyte clusters. (G) Neural morphology in the regenerating tentacle stained with the anti-FMRFamide antibody. Yellow arrows indicate neural fibers. (H) The regenerating tentacle is fully functional at 72 hpa. Image of the tentacle capturing prey, brine shrimp (white arrow). (I) The rate of functional tentacles across the regeneration time course. Intact: n = 40 (tentacles), 0–72 hpa: n = 36. (J) Tentacle regeneration process after removing the bulb from canals. Yellow arrow in (iv) indicates a nematocyte cluster. Dpa: day post-amputation. n = 117/219 (tentacles). Ra: radial canal, Ri: ring canal. (K) Scheme of tentacle regeneration without bulb. The numerical values that were used to generate the graphs in (I) can be found in S1 Data. Scale bars: (B–D, J) 1 mm, (F, Gi) 100 μm, (Gii) 50 μm.

https://doi.org/10.1371/journal.pbio.3002435.g001

Among cnidarians, polyp-type animals such as Hydra, Hydractinia, and Nematostella have been utilized as models to understand the mechanism of whole-body regeneration, including patterning, body axis formation, and mechanical responses [16–18]. After mid-gastric bisection in Hydra, cell proliferation of the stem cells, or i-cells, around the wound site is accelerated by Wnt3a produced from dying cells to generate blastema [19]. Upon decapitation of the colony polyp Hydractinia, i-cells remotely located in the body column migrate to the injury site to form blastema [20]. During head regeneration of the sea anemone Nematostella, 2 adult stem-like cell populations, fast-cycling cells in the body wall epithelium and slow-cycling cells in the mesenteries, migrate toward the amputation site to form blastema [21]. These studies suggest that the recruitment of resident stem cells to the injury site is a prerequisite for blastema formation after amputation of the body. However, it remains unclear whether repair-specific proliferative cells (RSPCs) constitute the cellular source of blastema during cnidarian regeneration.

In contrast to the sessile polyp stage, medusae, commonly called jellyfish, exhibit a more complex body structure that includes multiple types of muscle such as smooth and striated muscles, developed neural networks, and distinct organs and appendages, which together enable free swimming and avoidance behaviors [22,23]. While most sexually reproducing medusae do not clonally propagate like polyps, medusae can still regenerate various organs and appendages (e.g., manubrium, tentacle, umbrella, gonad, eye) after injury and reconstitute de novo structures after their removal [24–30]. A recent report using the hydrozoan jellyfish Clytia has suggested that, upon removal of the entire manubrium, i-cells and differentiated cells localized in neighboring organs migrate to the damage site through the canals, contributing to de novo manubrium regeneration [27]. Despite the importance of proliferating blastema cells in highly regenerative animals, the detailed mechanisms of organ and appendage regeneration in medusae, particularly the mechanism of blastema formation and its specific role are largely unknown.

The hydrozoan jellyfish Cladonema pacificum is an emerging jellyfish model that has been utilized to study development and physiology [31–33]. Because Cladonema allows for easy lab maintenance with its high spawning rate, it enables monitoring all life cycle stages and exploring organismal responses to different stimuli. The genus Cladonema is morphologically characterized by branched tentacles at the medusa stage (Fig 1B) [31,34–36]. The Cladonema medusa tentacle is primarily composed of bilayered epithelial tissues (epidermis and gastrodermis) that include muscle fiber, also called epitheliomuscular cells [23]: i-cells, neurons, and nematocytes are located in the epidermal layer while neurons and gland cells are located in the gastrodermal layer. Resident stem cells, i-cells, are localized at the basal side of the tentacle (tentacle bulb), and are thought to give rise to progenitors and differentiated cells during normal development and homeostasis [24,37]. The continuous growth and branching potential of the medusa tentacle makes it an attractive model to understand the mechanisms of appendage morphogenesis, growth, and regeneration in cnidarians.

In this study, we investigate the cellular mechanism of appendage regeneration using the Cladonema medusa tentacle. Establishing the Cladonema tentacle as an organ that can efficiently and functionally regenerate upon amputation, we show that highly proliferative cells accumulate at the injury site within 24 h to behave as blastema. Pulse-chase experiments using nucleoside analogs as well as dye labeling reveal that most blastema cells are not derived from resident stem cells but rather appear locally after damage. We further identify the role of blastema cells as the principal cellular source of the epithelium in the newly formed tentacle, while resident stem cells contribute to nematogenesis and tissue elongation during both homeostasis and regeneration. These results suggest the existence of 2 distinct proliferative cell populations: blastema as RSPCs and resident stem cells as homeostatic stem cells, both of which collectively enable functional tentacle regeneration. In a broader context, our findings highlight the diversification of blastema formation in non-bilaterian systems, providing an evolutionary insight into animal regeneration.

Fujita S, Takahashi M, Kumano G, Kuranaga E, Miura M, Nakajima Y-i (2023)
Distinct stem-like cell populations facilitate functional regeneration of the Cladonema medusa tentacle.
PLoS Biol 21(12): e3002435. https://doi.org/10.1371/journal.pbio.3002435

Copyright: © 2023 The authors.
Published by PLOS. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

The question for creationists is why did your putative designer fail to give humans the ability to regenerate limbs when it gave that ability to other species, including a jellyfish. It can’t have been incompetence because that would mean it isn’t omnipotent; it can’t have been amnesia because that would mean it isn’t omniscient, so it must have been by choice if you believe the creationist superstition. But that would mean it can't be omnibenevolent because the ability to regenerate a lost limb would reduce the suffering in the world, but it chose not to give us that ability; it chose to let us suffer.

So, it can't be all loving, but it can be malevolent. So, did it choose not to give us the ability to regenerate a lost limb because it prefers to see us suffer?

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Thank you for sharing!

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