Information

2.4: Regeneration - Biology

2.4: Regeneration - Biology



We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Regeneration is the ability to replace lost or damaged body parts. This ability varies greatly among living things.

Plants

Plants can regenerate all body parts from precursor cells. Many trees, for example, can be cut off at the ground and, in due course, sprouts appear at the margins of the stump. These go on to develop new stems, leaves, and flowers. In the laboratory, entire plants can develop from a mass of undifferentiated cells growing in culture.

Figure (PageIndex{i}): Carrot plant grown in a laboratory courtesy of Roy De Carava and Scientific American

For example, a fully-differentiated carrot root cell when grown in a suitable culture medium, begins to divide repeatedly, losing its differentiated structure as it does so. Then its descendants begin to differentiate, and they finally form all the organs of a mature carrot plant. The above photo shows a carrot plant that grew in a flask from fully-differentiated root cells that had been isolated and induced to undergo mitosis.

Invertebrate Animals

Sponges

Sponges can regenerate the entire organism from just a conglomeration of their cells.

Hydra

This cnidarian can also regenerate its entire body from cells. The cells that do the job are totipotent stem cells residing in the animal's body.

Planarians

Figure (PageIndex{i}): Dugesia and Dugesia regenaration

When some species of flatworms (left) are decapitated, they can regenerate a new head. Double-amputees can regenerate both a new head at the anterior surface and a new tail at the posterior surface (right). They do this by the proliferation and differentiation of the pluripotent stem cells (called neoblasts) that it retains in its body throughout its life.

How do the cells know whether to develop into a head or a tail? Thanks to the ease with which individual genes can be knocked out by RNA interference (RNAi), it has been shown that Wnt/β-catenin signaling dictates where the head and tail form.

  • Blocking Wnt/β-catenin signaling by RNAi causes a head to form where a tail should (producing a two-headed animal) while
  • blocking part of the β-catenin degradation complex (thus enhancing the pathway) causes a tail to develop where a head should (producing a two-tailed animal).

Thus it appears that the default pathway of neoblasts is to regenerate a head. In the amputated animal, a gradient of Wnt/β-catenin signaling extends from a high in the posterior — leading to the formation of a tail — and decreasing towards the anterior until the default pathway is no longer inhibited and a head can form.

Sea Stars (aka "Starfish')

Figure (PageIndex{i}): Sea star regenerating an arm courtesy of Dr. Charles Walcott

These echinoderms can regenerate the entire organism from just one arm and the central disk. I have read that at one time oyster fishermen used to dredge up sea stars from their oyster beds, chop them up in the hope of killing them, and then dump the parts back overboard. They soon discovered to their sorrow the remarkable powers of regeneration of these animals.

Vertebrates

Newts and Salamanders

Figure (PageIndex{i}): Salamander

These amphibians can regenerate a missing tail, legs, even eyes. This remarkable ability is particularly pronounced in the larval stage. For this reason, larval salamanders are favorites for doing research on regeneration. For example, cutting the tail off a larval salamander initiates the following sequence of events:

  • A layer of epidermal cells grows over and covers the stump.
  • A mass of undifferentiated cells — called the blastema — develops just beneath.
  • Muscle and cartilage form in the regrowing tail.
  • The notochord and spinal cord grow out into the regrowing tail.
  • After a few weeks, a new, fully-functional and anatomically-correct tail is complete.

The Mechanism

For years, it has been unclear as to whether this regeneration depends on

  • a population of pluripotent stem cells that have resided in the animal body prepared for such an event (as occurs in the hydra) or
  • the dedifferentiation of specialized cells, e.g. muscle and cartilage cells, in the stump.

The answer appears to be both.

  • Stem cells in the spinal cord migrate into the regrowing tail and differentiate into several cell types, including muscle and cartilage. Although the stem cells are ectoderm, they are able to develop into mesoderm.
  • Muscle cells in the stump migrate into the blastema while
    • reentering the cell cycle to produce thousands of descendants;
    • dedifferentiate as they do so; that is, they lose the characteristic proteins, etc. of muscle cells.
  • Even though there is as yet no sign of a tail, its final pattern is established during this process for if the blastema is removed and transplanted elsewhere, it will continue the process of regenerating a tail.
  • Finally the cells of the blastema differentiate into all the cell types — nerve, muscle, cartilage, skin — used to build the regenerated tail.

Mammals

Don't we wish that we had the same powers of regeneration that salamanders do: able to regenerate a severed spinal cord or grow a new heart! But unfortunately, we cannot. We can regenerate some skin, a large amount of liver, and the very tips of fingers and toes. But that's about it. Just why we are so limited is not known (but is the subject of intense research). Much of the excitement surrounding research on stem cells is because of the hope that they may provide a means of regrowing damaged or lost tissues or even organs.

In contrast to the situation that appears to hold for salamanders, dedifferention of specialized cells does not appear to play a role in the formation of a blastema in mice. Instead, the various tissues — epidermis, hair follicles, sweat glands, neurons (all ectoderm) and muscle, bone, tendon, blood vessels (mesoderm) — that participate in regenerating the tip of an amputated mouse digit (finger or toe) develop from a diverse population of "adult" stem cells in the stump that retain their restricted developmental potential. You can read about the evidence for this in Rinkevich, Y., et al., Nature, 476, 409-413 (25 August 2011).

Genetic Control of Regeneration

A number of genes have been found to be implicated in regeneration. One of the most potent of these is Wnt.

  • Injection of agents (e.g. antisense RNA molecules) that interfere with the Wnt/β-catenin pathway
    • blocks limb regeneration in salamanders and, as we saw above,
    • promotes head formation in regenerating planarians, while
  • injection of agents that enhance the Wnt/β-catenin pathway
    • enable chicks (that, like mammals, are normally incapable of regenerating limbs) to regenerate a wing;
    • as well as enabling a regenerating planarian to form a tail where a head should go.

2.4: Regeneration - Biology

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited.

Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review prior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involves several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest progress in the field that systematically reviews the most exciting advances in scientific literature. This type of paper provides an outlook on future directions of research or possible applications.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.


MDI Biological Laboratory scientist identifies signaling underlying regeneration

BAR HARBOR, MAINE — Many salamanders can readily regenerate a lost limb, but adult mammals, including humans, cannot. Why this is the case is a scientific mystery that has fascinated observers of the natural world for thousands of years.

Now, a team of scientists led by James Godwin, Ph.D., of the MDI Biological Laboratory in Bar Harbor, Maine, has come a step closer to unraveling that mystery with the discovery of differences in molecular signaling that promote regeneration in the axolotl, a highly regenerative salamander, while blocking it in the adult mouse, which is a mammal with limited regenerative ability.

"Scientists at the MDI Biological Laboratory have been relying on comparative biology to gain insights into human health since its founding in 1898," said Hermann Haller, M.D., the institution's president. "The discoveries enabled by James Godwin's comparative studies in the axolotl and mouse are proof that the idea of learning from nature is as valid today as it was more than one hundred and twenty years ago."

Instead of regenerating lost or injured body parts, mammals typically form a scar at the site of an injury. Because the scar creates a physical barrier to regeneration, research in regenerative medicine at the MDI Biological Laboratory has focused on understanding why the axolotl doesn't form a scar - or, why it doesn't respond to injury in the same way that the mouse and other mammals do.

"Our research shows that humans have untapped potential for regeneration," Godwin said. "If we can solve the problem of scar formation, we may be able to unlock our latent regenerative potential. Axolotls don't scar, which is what allows regeneration to take place. But once a scar has formed, it's game over in terms of regeneration. If we could prevent scarring in humans, we could enhance quality of life for so many people."

The axolotl as a model for regeneration

The axolotl, a Mexican salamander that is now all but extinct in the wild, is a favorite model in regenerative medicine research because of its one-of-a-kind status as nature's champion of regeneration. While most salamanders have some regenerative capacity, the axolotl can regenerate almost any body part, including brain, heart, jaws, limbs, lungs, ovaries, spinal cord, skin, tail and more.

Since mammalian embryos and juveniles have the ability to regenerate - for instance, human infants can regenerate heart tissue and children can regenerate fingertips - it's likely that adult mammals retain the genetic code for regeneration, raising the prospect that pharmaceutical therapies could be developed to encourage humans to regenerate tissues and organs lost to disease or injury instead of forming a scar.

In his recent research, Godwin compared immune cells called macrophages in the axolotl to those in the mouse with the goal of identifying the quality in axolotl macrophages that promotes regeneration. The research builds on earlier studies in which Godwin found that macrophages are critical to regeneration: when they are depleted, the axolotl forms a scar instead of regenerating, just like mammals.

The recent research found that although macrophage signaling in the axolotl and in the mouse were similar when the organisms were exposed to pathogens such as bacteria, funguses and viruses, when it came to exposure to injury it was a different story: the macrophage signaling in the axolotl promoted the growth of new tissue while that in the mouse promoted scarring.

The paper on the research, entitled "Distinct TLR Signaling in the Salamander Response to Tissue Damage" was recently published in the journal Developmental Dynamics. In addition to Godwin, authors include Nadia Rosenthal, Ph.D., of The Jackson Laboratory Ryan Dubuque and Katya E. Chan of the Australian Regenerative Medicine Institute (ARMI) and Sergej Nowoshilow, Ph.D., of the Research Institute of Molecular Pathology in Vienna, Austria.

Godwin, who holds a joint appointment with The Jackson Laboratory, was formerly associated with ARMI and Rosenthal is ARMI's founding director. The MDI Biological Laboratory and ARMI have a partnership agreement to promote research and education on regeneration and the development of new therapies to improve human health.

Specifically, the paper reported that the signaling response of a class of proteins called toll-like receptors (TLRs), which allow macrophages to recognize a threat such an infection or a tissue injury and induce a pro-inflammatory response, were "unexpectedly divergent" in response to injury in the axolotl and the mouse. The finding offers an intriguing window into the mechanisms governing regeneration in the axolotl.

Being able to 'pull the levers of regeneration'

The discovery of an alternative signaling pathway that is compatible with regeneration could ultimately lead to regenerative medicine therapies for humans. Though regrowing a human limb may not be realistic in the short term, significant opportunities exist for therapies that improve clinical outcomes in diseases in which scarring plays a major role in the pathology, including heart, kidney, liver and lung disease.

"We are getting closer to understanding how axolotl macrophages are primed for regeneration, which will bring us closer to being able to pull the levers of regeneration in humans," Godwin said. "For instance, I envision being able to use a topical hydrogel at the site of a wound that is laced with a modulator that changes the behavior of human macrophages to be more like those of the axolotl."

Godwin, who is an immunologist, chose to examine the function of the immune system in regeneration because of its role in preparing the wound for repairs as the equivalent of a first responder at the site of an injury. His recent research opens the door to further mapping of critical nodes in TLR signaling pathways that regulate the unique immune environment enabling axolotl regeneration and scar-free repair.

Godwin's research is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant numbers P20GM103423 and P20GM104318 to the MDI Biological Laboratory. ARMI is supported by grants from the State Government of Victoria, Australia. The mouse studies were supported by Jackson Laboratory institutional funds.

About the MDI Biological Laboratory

We aim to improve human health and healthspan by uncovering basic mechanisms of tissue repair, aging and regeneration, translating our discoveries for the benefit of society and developing the next generation of scientific leaders. For more information, please visit mdibl.org.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.


Learn more: Fasting-mimicking diet

  • A low-calorie fasting-like diet, plus chemotherapy, enables the immune system to recognize and kill skin and breast cancer cells, according to a new USC-led study on mice.
  • Evidence is mounting that a diet mimicking the effects of fasting has health benefits beyond weight loss, with a new USC-led study indicating that it may reduce symptoms of multiple sclerosis.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as people age. By outlining how prolonged fasting cycles — periods of no food for two to four days at a time over the course of six months — kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

“We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system,” said corresponding author Valter Longo, Edna M. Jones Professor of Gerontology and the Biological Sciences at the USC Davis School of Gerontology and director of the USC Longevity Institute. Longo has a joint appointment at the USC Dornsife College of Letters, Arts and Sciences.

“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged,” Longo said. “What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?”

Fasting cycles

Prolonged fasting forces the body to use stores of glucose, fat and ketones, but it also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency — that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system,” explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune system. “And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy, extending Longo’s influential past research.

“While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy,” said co-author Tanya Dorff, assistant professor of clinical medicine at the USC Norris Comprehensive Cancer Center and Hospital. “More clinical studies are needed, and any such dietary intervention should be undertaken only under the guidance of a physician.”

“We are investigating the possibility that these effects are applicable to many different systems and organs, not just the immune system,” said Longo, whose lab is in the process of conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.

The study was supported by the National Institute of Aging of the National Institutes of Health (grant numbers AG20642, AG025135, P01AG34906). The clinical trial was supported by the V Foundation and the National Cancer Institute of the National Institutes of Health (P30CA014089).

Chia Wei-Cheng of USC Davis was first author of the study. Gregor Adams, Xiaoying Zhou and Ben Lam of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC Laura Perin and Stefano Da Sacco of the Saban Research Institute at Children’s Hospital Los Angeles Min Wei of USC Davis Mario Mirisola of the University of Palermo Dorff and David Quinn of the Keck School of Medicine of USC and John Kopchick of Ohio University were co-authors of the study.

More stories about: Diet, Stem Cells


In vitro regeneration, antioxidant potential, and genetic fidelity analysis of Asystasia gangetica (L.) T.Anderson

An effective protocol for the plant regeneration via direct and indirect organogenesis has been developed from leaf explants of Asystasia gangetica (L.), cultured on Murashige and Skoog (MS) medium supplemented with various concentrations and combinations of auxin and cytokinins. Approximately 86% of explants produced direct shoots on MS medium containing 0.5 mg L −1 6-benzyladenine (BA) and 10 μg L −1 Triacontanol (TRIA) with a maximum of 4.82 ± 0.29 shoots per leaf segment. For production of callus-mediated plantlets (indirect), primarily callus was induced on MS medium containing 2 mg L −1 2,4-dichlorophenoxyacetic acid (2,4-D), which was then subcultured on medium with 0.1 mg L −1 naphthaleneacetic acid (NAA), 0.5 mg L −1 BA, and 1 to 8 mg L −1 2-isopentenyl adenine (2iP) in order to develop organogenic callus and subsequent shoot induction. A maximum of 6.84 ± 0.05 shoots per callus clump was obtained on MS media supplemented with 4 mg L −1 2iP, 0.5 mg L −1 BA, and 0.1 mg L −1 NAA. The shootlets produced roots when cultured on half-strength MS media supplemented with 2 mg L −1 indole-3-butyric acid (IBA). In vitro propagated plantlets were hardened on soil rite and acclimatized to field condition with 85% survivability. The chlorophyll content of acclimatized plants was comparable with that of the mother plant, while stomatal micromorphology of regenerated plants exhibited no abnormalities. The radical scavenging and antioxidant activity of methanolic extract of leaves were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP), and phosphomolybdenum test. In all experiments, regenerated plants exhibited enhanced antioxidant potential indicating micropropagated plants could be exploited for isolation of novel biomolecules. Further, the genetic homogeneity of acclimatized plants was confirmed by PCR-based start codon targeted (SCoT) markers and ycf1b DNA barcoding primers which exhibited monomorphic bands identical to the normal mother plant and no variations were observed.

This is a preview of subscription content, access via your institution.


Neurogenesis, axonogenesis and the ependymal tube: restoring the nervous system

Restoring the spinal cord in the regenerated tail

Tail regeneration involves not only outgrowth of the cartilaginous skeleton, but also the re-establishment of the spinal cord. In lizards (as well as salamanders), the spinal cord passes from the base of the brain to almost the tip of the tail. In contrast, amongst mammals, the spinal cord terminates cranial to the pelvis and never enters the tail. Along its entire length, the lizard spinal cord demonstrates a conserved morphology, essentially identical to that of mammals: a central canal (continuous with the ventricular system of the brain) encircled by a sleeve or tube of ependymal cells, surrounded by grey matter (neuronal cell bodies) and white matter (nerve tracks) (Fig. 3A). At regular intervals, the spinal cord is flanked by dorsal root ganglia and spinal nerves. During tail autotomy, the spinal cord and spinal nerves are severed. Within days, outgrowth of the regenerate spinal cord begins as ependymal cells near the site of rupture first proliferate and then assemble into the tube-like structure enclosing the central canal (McLean and Vickaryous, 2011). Ependymal tube outgrowth is closely matched by axonogenesis, the regrowth of severed axons. Newly formed nerve tracts originate from dorsal root ganglia in the remaining tail stump and descending tracts from the white matter of the original spinal cord (Bellairs and Bryant, 1985) (Fig. 3B). Conspicuously, the regenerated spinal cord does not contain grey matter, nor is there any restoration of dorsal root ganglia in the new tail all the replacement innervation appears to originate from more proximal neuronal structures (Bellairs and Bryant, 1985). Although this stands in stark contrast to the situation in salamanders, wherein the spinal cord and dorsal root ganglia are near-perfectly replaced during tail regeneration (Mchedlishvilli et al., 2012), it is worth noting that the regenerated lizard tail is fully functional (Arnold, 1984 Bellairs and Bryant, 1985). Like the original appendage, if regenerated tails are autotomized, they too are capable of vigorous independent movements to distract predators (Meyer et al., 2002).

Renewing the nervous system. Although tail-autotomizing lizards such as Eublepharis macularius (leopard gecko) can restore the spinal cord during tail regeneration, the replacement lacks the fidelity of the original. (A) As for other lizards, the original spinal cord of the tail consists of a tubular arrangement of ependymal cells (enclosing the central canal), surrounded by grey matter (invested with neuronal cell bodies) and white matter (nerve tracts labelled by RT97). (B) The fully regenerated spinal cord includes the ependymal tube and white matter, but conspicuously lacks grey matter. (C) Schematic illustration of a leopard gecko brain. (D) A representative transverse section through the left telencephalon. (E) Radial glia (labelled here with GFAP) within the ventricular zone serve as the self-renewing source of new neurons, and provide scaffolds for neuroblast migration. Once neuroblasts arrive in the cellular layer of the medial cortex, they become neurons. Abbreviations: cb, cerebellum DAPI, 4′-6-diamino-2-phenylidole (nuclear marker) di, diencephalon et, ependymal tube GFAP, glial fibrillary acid protein (radial glia cell marker) gm, grey matter ipl, inner plexiform layer lv, lateral ventricle mc, medial cortex ob, olfactory bulb ot, optic tectum sc, spinal cord RT97, neurofilament marker tel, telencephalon vz, ventricular zone wm, white matter. All scale bars, 10 μm (except D, 50 μm).

Renewing the nervous system. Although tail-autotomizing lizards such as Eublepharis macularius (leopard gecko) can restore the spinal cord during tail regeneration, the replacement lacks the fidelity of the original. (A) As for other lizards, the original spinal cord of the tail consists of a tubular arrangement of ependymal cells (enclosing the central canal), surrounded by grey matter (invested with neuronal cell bodies) and white matter (nerve tracts labelled by RT97). (B) The fully regenerated spinal cord includes the ependymal tube and white matter, but conspicuously lacks grey matter. (C) Schematic illustration of a leopard gecko brain. (D) A representative transverse section through the left telencephalon. (E) Radial glia (labelled here with GFAP) within the ventricular zone serve as the self-renewing source of new neurons, and provide scaffolds for neuroblast migration. Once neuroblasts arrive in the cellular layer of the medial cortex, they become neurons. Abbreviations: cb, cerebellum DAPI, 4′-6-diamino-2-phenylidole (nuclear marker) di, diencephalon et, ependymal tube GFAP, glial fibrillary acid protein (radial glia cell marker) gm, grey matter ipl, inner plexiform layer lv, lateral ventricle mc, medial cortex ob, olfactory bulb ot, optic tectum sc, spinal cord RT97, neurofilament marker tel, telencephalon vz, ventricular zone wm, white matter. All scale bars, 10 μm (except D, 50 μm).

Neurogenesis in the lizard brain

Physiological neurogenesis

It is now widely recognized that all adult vertebrates can generate new neurons, a process known as physiological neurogenesis (see Glossary Kaslin et al., 2008). In mammals, physiological neurogenesis is restricted to two discrete areas: the subventricular zone (SVZ) of cerebral cortex and the subgranular zone of the dentate gyrus (Kaslin et al., 2008). However, for many non-mammalian vertebrates, including teleost fish (Kizil et al., 2012 Zupanc, 2001), salamanders (Maden et al., 2013), various birds (Alvarez-Buylla et al., 1994) and lizards (e.g. Perez-Cañellas and García-Verdugo, 1996 Marchioro et al., 2005 see Font et al., 2001), physiological neurogenesis routinely occurs within many areas of the brain. Among lizards, these neurogenic areas include several regions of the telencephalon (e.g. dorsal and lateral cerebral cortex, anterior dorsal ventricular ridge, nucleus sphericus), as well as the olfactory bulb and cerebellum (Font et al., 2001). However, physiological neurogenesis is best understood for the medial (cerebral) cortex (Fig. 3C–E), the equivalent of the mammalian dentate gyrus (and likely involved in place learning and relational memory see Naumann et al., 2015). New neurons are generated a short distance away from the medial cortex, in the adjacent ventricular zone (VZ). The VZ is a pseudostratified epithelium that lines the ventricular system of the brain (Fig. 3D,E). Although the VZ of reptiles is distinct from the better-known SVZ of mammals, the two regions appear to serve similar roles as proliferative neurogenic niches (García-Verdugo et al., 2002 Kaslin et al., 2008). The main cell types residing within the VZ are ependymal cells and radial glia (see Glossary also called ependymoradial glia). Radial glia are generally accepted as the precursor or source population of new neurons (Delgado-Gonzalez et al., 2011). The most likely scenario is that radial glia within the VZ undergo asymmetrical cell division, thereby self-renewing and giving rise to a migratory daughter cell or neuroblast. Neuroblasts then travel into the cortices to differentiate, and become structurally mature (and presumably fully functional) neurons.

Whereas physiological neurogenesis may be a relatively common phenomenon among lizards, evidence indicates that, at least in some species, it is seasonally variable (a phenomenon also reported for songbirds Brenowitz and Larson, 2015). For example, neurogenesis associated with the olfactory system of Gallotia galloti (Gallot's lizard) demonstrates a significant decrease in the number of neuroblasts migrating to the olfactory bulbs during the summer (Delgado-Gonzalez et al., 2011). Based on these observations, it is possible that G. galloti exhibits a corresponding seasonal fluctuation in olfactory abilities – an intriguing prediction that deserves further investigation. The same study also reported that the time frame for the completion of neurogenesis was much longer in G. galloti (90 days) than for other species (e.g. 7 days in Podarcis hispanicus, the Iberian wall lizard Lopez-Garcia et al., 1990). Whether this comparative delay reflects species-specific variation or is the result of differences in (for example) the chronological age of the experimental animals (the G. galloti studied were ∼6 years old the age of P. hispanicus was not specified) remains uncertain (Molowny et al., 1995 Delgado-Gonzalez et al., 2011).

Compensatory neurogenesis

In addition to constitutive neurogenesis, at least some teleost fish, salamander and lizard species are also proficient at generating new neurons in response to brain injuries, so-called compensatory neurogenesis (Font et al., 1991, 1997 Kizil et al., 2012 Maden et al., 2013). In lizards, the antimetabolite 3-acetylpyridine (3AP, a nicotinamide antagonist) has been used to chemically target neurons in the cellular layer of the medial cortex. Using P. hispanicus, a single treatment with 3AP causes 34–97% of the neurons in the medial cortex to undergo apoptosis (Font et al., 1991, 1997). Treated lizards quickly develop a suite of behavioural changes consistent with neurotoxicity, as well as problems with spatial memory performance and capturing prey (although not with walking or eating Font et al., 1991, 1997). Within 10 days following treatment, the behavioural impairments are no longer obvious, and by 42–49 days post-treatment the populations of neurons within the medial cerebral cortex appear to be almost restored. Curiously, while compensatory neurogenesis restores the heavily lesioned medial cerebral cortex within 7 weeks, restoration of neurons to an adjacent area (the dorsomedial cortex), which by comparison is only modestly damaged by 3AP treatment, is more variable (Font et al., 1997).

Building on these findings, the capacity for compensatory neurogenesis to repair a physical lesion (an incision to the dorsal cortex) has also been explored in G. galloti (Romero-Alemán et al., 2004). Within days, proliferating immune cells of the central nervous system (microglia and macrophages) are observed at the wound site. In the following 2–4 weeks, proliferation is additionally upregulated at the VZ adjacent to the injury. This marked increase in proliferation persists for 240 days, suggesting ongoing tissue restoration, though immune cells return to baseline numbers during this time. To date, the full extent to which the lizard brain can regenerate from a direct physical lesion is unclear.

Restoring the optic nerve

Another region of the central nervous system demonstrating variable responses to injury is the optic nerve. The optic nerve consists of axons from retinal ganglion cells, which integrate and relay visual information from the retina of the eye to visual centres in the brain (Fischer and Leibinger, 2012 Wang et al., 2012). In mammals and birds, damage to these axons can result in vision loss, as retinal ganglion cells degenerate and undergo cell death (Lang et al., 1998, 2017 Williams, 2017). Cellular degeneration and the inability to restore the visual pathway in these species appears to be the result of a complex inhibitory microenvironment, related to the formation of a glial scar (rich in proteoglycans and glial cells) and various axon-impeding proteins such as Nogo-A (Dunlop et al., 2004 Lang et al., 2017). As might be expected, species capable of restoring vision after injury to the optic nerve (e.g. zebrafish) are characterized by retinal ganglion cell survival (Zou et al., 2013), and the absence of axon inhibitory proteins such as Nogo (Abdelesselem et al., 2009) and a glial scar (Bollaerts et al., 2017). Paradoxically, the optic nerve of some lizard species can regenerate, even though they express Nogo-A and form a glial scar (Lang et al., 1998, 2017). Optic nerve regeneration is particularly efficient in Ctenophorus ornatus (the ornate dragon lizard), with the crushed optic nerve outgrowing to re-contact the optic tectum within 1 month (Beazley et al., 1997 Dunlop et al., 2004). Although excitatory and inhibitory neurotransmission is dysfunctional following regeneration, and vision is not spontaneously returned, lizards can regain sight with training (Beazley et al., 2003). One explanation, based on in vitro experiments, is that retinal ganglion cells of lizards are insensitive to the inhibitory signals that otherwise obstruct mammalian axon outgrowth. Using an explant strategy, mammalian (rat) dorsal root ganglia and lizard (Gallot's lizard) retina were cultured on each of mammalian and lizard glial cells. Whereas both these environments inhibited regrowth of mammalian axons, neither inhibited the regrowth of lizard axons (Lang et al., 1998). Combined, these data reveal a surprising diversity across vertebrates in how the optic nerve responds to injury, with lizards uniquely interposed between full functional restoration and regenerative failure.


Abstract

Methods are described for the enzymatic release of protoplasts from leaves of Petunia hybrida and for the utilization of protoplasts in studies in plant developmental biology. As a result of spontaneous fusion during cell wall degradation of leaf material, fresh preparations can contain a high proportion of multinucleate protoplasts. This level can be dramatically reduced by a gradual plasmolysis of the material prior to enzyme incubation.

Leaf protoplasts maintained in liquid media are seen to undergo cell wall synthesis, “budding,” and limited regenerated cell division sometimes associated with anthocyanin production. Under such conditions, multinucleate cells are formed as a result of mitosis without cytokinesis.

Protoplasts, plated out in a fully defined medium, undergo cell wall synthesis followed by sustained progeny cell division with eventual cell colony production. Cell colonies, derived from individual mesophyll protoplasts, grow rapidly upon subculture, to produce callus capable of shoot differentiation and ultimately whole plant formation. Protoplasts isolated from varieties of P. hybrida were found to differ in their cultural requirements.

This work was supported by a grant from the Agricultural Research Council.


[WEBINAR] 2, 4 & 7 June 2021: The role of the Solidarity Economy to enhance the impact of NBS in urban regeneration projects

On 2, 4 & 7 June: URBiNAT is hosting an Online Seminar Series on the role of the Solidarity Economy to enhance the impact of NBS being implemented as part of urban regeneration programmes.

Discussions will look at how the NBS concept can be expanded to take into account the social and solidarity economy NBS, and recognize the importance of the solidarity economy in times of crises and uncertainty.

The conceptual foundation of the URBiNAT is based on active involvement of citizens in the development and implementation of Nature-based Solutions. Through participatory processes, the co-creation of NBS have a beneficial impact on the environment but also on the well-being and economic situation of citizens.

The solidarity economy, in its various forms, is viewed as a means to reduce economic inequalities. Solutions include solidarity markets, social currencies, short food supply chains, and solidarity purchase groups.

The Seminar Series will take place over three days, with debates and presentations made by URBiNAT cities:

  • Part 1: Urban public space: commons, justice and social reproduction
  • Part 2: The socio-economy practices for neighbourhoods revitalisation
  • Part 3: The sustainability of nature-based solutions and solidarity economy

The Seminar will involve partners and cities working on socio-economic issues to share knowledge and experience gather experts from university, research centres, international network and URBiNAT scientific commission also, the sisters’ projects to dialogue with us, namely sharing their best practices in the solidarity economy dimensions. After the Seminar, the URBiNAT intends to organize a special edition of the CES context edition, periodical publication from CES to disseminate the reflection and debate results.

URBiNAT recognizes the social and solidarity economy as an opportunity to build a different urban space and to analyse its complexity. In fact, the project assumes it as one of the dimensions for the implementation of nature-based solutions (NBS). The functionality of public spaces can expand with solidarity economy initiatives, diversifying the way citizens use the urban spaces. SE reveals a strong territoriality and connection to physical space – it may range from individual self-provisioning and informal small-scale economic circuits localized and operating within a limited territorial scope to networking on a larger area (region or national level). In some cases, territoriality is linked to culture, thus enabling community culture to develop territorial identity circuits.

The Online Seminar Series is organized in a multi-stakeholder and co-production perspective. Different audiences could participate and engage in this knowledge sharing space, citizens, technicians, political representatives, researchers, practitioners.


Author Contributions

TG collectedand cultured the animals, performed the regeneration, and EdU experiments, as well as the light and confocal microscopy, drew the figures, carried out the statistical analysis, and prepared the histological sections. TG and LM analyzed the histological sections and microscopy images and interpreted the regeneration processes. AKU and DH performed the transcriptome and phylogenetic analyses. TG and NS conceived the study and interpreted the data. NS supervised the study and drafted the manuscript together with TG. All authors contributed to the article and approved the submitted version.


Ya-Chieh Hsu, Ph.D.

Skin, the largest organ we have, protects us from insults and dehydration, and facilitates sensory perception and thermoregulation. These multifaceted functions are accomplished by a rich diversity of cell types within the skin. Throughout life, the epidermis and its appendages, the hair follicles, possess remarkable capacity to renew themselves during homeostasis and to heal themselves upon injury. These features necessitate multiple resident reservoirs of stem cells. Together, the skin represents an ideal paradigm for studying stem cells and their interactions with surrounding microenvironments, or niches.

We use a wide variety of approaches and techniques, including molecular, cellular, genetic and genomic tools, to investigate how stem cell behaviors are regulated by their downstream progeny, their niches, and at systemic level. We aim to understand how these regulations occur in a precise manner to meet various physiological demands, how communications between stem cells and their niches facilitate an organ to adapt, and how dysregulated stem cell behaviors lead to diseases.

Skin is our primary model system, but we are also exploring other epithelial tissues to determine the extent to which these mechanisms are shared or separate.

Biosketch

Ya-Chieh Hsu is the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard University, and a Principal Faculty Member at the Harvard Stem Cell Institute. She is supported by a K99-R00 pathway to independence award from NIH, and is a past recipient of the Starr Stem Cell Foundation Fellowship and the NYSCF-Druckenmiller Fellowship.


Watch the video: Stem Cells and Tissue Regeneration: Planarians (August 2022).