Model systems for regeneration: planarians

Ivanković, Mario; Haneckova, Radmila; Thommen, Albert; Grohme, Markus A.; Vila‐Farré, Miquel; Werner, Steffen; Rink, Jochen C.

doi:10.1242/dev.167684

Cited by 100 publications

(83 citation statements)

References 150 publications

(189 reference statements)

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“…The rate of brain regeneration that we observed was consistent with results from other research groups in various planarians species (Reviewed in Birkholz et al, 2019;Brown andPearson, 2017, Cebrià 2007;Cebrià et al, 2018;Fraguas et al, 2012;Inoue et al, 2004;Ivankovic et al, 2019;Ross et al, 2017). Our experiments show that intact planarians, as expected, displayed a constant response to 1 mM cytisine exposure over a period of nine days, in contrast to decapitated planarians, which did not significantly respond to this cytisine treatment until day four, when they began to display pSLMs, indicating a gradual recovery of function, which was complete by day 9 (Fig.…”

Section: Cytisinesupporting

confidence: 91%

“…Several species of freshwater planarians are established model invertebrates in regeneration and developmental biology research (Cebrià et al, 2002(Cebrià et al, , 2018(Cebrià et al, , 2019Ivankovic et al, 2019;Gentile et al, 2011;Li et al, 2015). One of the most distinct advantages of the planarian model system is that many planarians species display a remarkable ability shared by very few other organisms: the capacity for complete (and correct) regeneration of their nervous system upon injury or even full decapitation (Cebrià, 2007(Cebrià, , 2008(Cebrià, , 2019Gentile et al, 2011;Owlarn and Bartscherer, 2016;Ross et al, 2017;Umesono et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Measuring functional brain recovery in regenerating planarians by assessing the behavioral response to the cholinergic compound cytisine

Pagán

Baker²,

Deats³

et al. 2020

Int. J. Dev. Biol.

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Planarians are traditional model invertebrates in regeneration and developmental biology research that also display a variety of quantifiable behaviors useful to screen for pharmacologically active compounds. One such behavior is the expression of seizure-like movements (pSLMs) induced by a variety of substances. Previous work from our laboratory showed that cocaine, but not nicotine, induced pSLMs in intact but not decapitated planarians. Interestingly, as decapitated planarians regenerated their heads, they gradually recovered their sensitivity to cocaine. These results suggested a method to assess planarian brain regeneration and a possible way of identifying compounds that could enhance or hold back brain regeneration. In the present work, we demonstrate that the cholinergic agent cytisine is a suitable reference compound to apply our method. Cytisine induces pSLMs in a concentration-dependent manner in intact (but not decapitated) planarians of the species Girardia tigrina. Based on our data, we developed a behavioral protocol to assess planarian brain regeneration over time. We tested this method to measure the effect of ethanol on G. tigrina’s brain regeneration. We found that ethanol slows down the rate of planarian brain regeneration in a concentration-dependent manner, consistently with data from other research groups that tested ethanol effects on planarian brain regeneration using different behavioral protocols. Thus, here we establish a general method using cytisine-induced pSLMs as an indicator of brain regeneration in planarians, a method that shows potential for assessing the effect of pharmacologically active compounds in this process.

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Section: Cytisinesupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Measuring functional brain recovery in regenerating planarians by assessing the behavioral response to the cholinergic compound cytisine

Pagán

Baker²,

Deats³

et al. 2020

Int. J. Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In fact, a whole individual can be regenerated from just a tiny piece of the worm; and when planarians are cut in half, regeneration occurs from both wound sites to reconstitute their respective missing body sections. Out of all the planarians, Schmidtea mediterranea and Dugesia japonica are the most studied species, since both show robust regeneration capabilities (Ivankovic et al 2019;Newmark and Sánchez Alvarado 2002). However, other species of planarians have more restricted abilities, or even none at all.…”

Section: Planarianmentioning

confidence: 99%

“…As recently reviewed, polarity cues, in addition to tissue-resident positional information, may generate a unique signaling milieu at the wound site that will influence cell fate specification of both arriving neoblasts and their progeny (Ivankovic et al 2019;Reddien 2018).…”

Section: Planarianmentioning

confidence: 99%

Basics of Self-Regeneration

Aires

Keeley

Sandoval-Guzmán

2020

Reference Series in Biomedical Engineering

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Regeneration is a fascinating phenomenon spanning several levels of complexity, allowing organisms to repair, renew, and reconstitute missing or damaged parts. Despite significant efforts to understand regeneration, the lack of adequate technology has slowed advances in the field until very recently. Since the beginning of the eighteenth century, scientists have looked toward animal models while striving to dissect the cellular and molecular pathways that drive regeneration. Although we are still far from the day that humans could regenerate an appendage, several mechanisms used by other animal species have been uncovered. This knowledge brings us closer to their potential transfer to humans, enabling the repair of specific tissues. Even though regeneration occurs in many organisms, the extent of this trait varies enormously: planarian worms can regenerate their whole body and are even able to create two new worms from a bisected individual, whereas mammals can only regenerate specific parts of an organ or tissue, such as the very distal tip of a digit. Among vertebrates, however, salamanders are able to regenerate complex structures such limbs or tails, making them the object of intense scientific research. This chapter addresses limb regeneration using one specific species of salamanderthe axolotlas an example of a complex structure that is reformed from cells of different embryonic origins. It also discusses the advances in technology that allow the pursuit and answering of important questions within this topic, and includes a brief look into the future and what remains to be explored in the field.

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“…The freshwater planarian Schmidtea mediterranea is an ideal model organism to study how injury invokes repair due to their virtually endless ability to regenerate (Ivankovic et al, 2019). This ability is driven by an abundant, heterogeneous population of stem cells (Adler & Sánchez Alvarado, 2015;Reddien, 2018;Zhu & Pearson, 2016).…”

Section: Introductionmentioning

confidence: 99%

Planarian stem cells sense the identity of missing tissues to launch targeted regeneration

Bohr

Shiroor

Adler

2020

Preprint

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In order to regenerate tissues successfully, stem cells must first detect injuries and then produce missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare stem cell responses to different injuries by amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing: loss of non-pharyngeal tissues increases numbers of non-pharyngeal progenitors, while removal of the pharynx specifically triggers proliferation and expansion of pharynx progenitors. By pharmacologically inhibiting either proliferation or activation of the MAP kinase ERK, we identify a narrow window of time during which proliferation, followed by ERK signaling, produces pharynx progenitors necessary for regeneration. Further, unlike pharynx regeneration, eye regeneration does not depend on proliferation or ERK activation. These results indicate that stem cells tailor their proliferation and expansion to match the regenerative needs of the animal.

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Model systems for regeneration: planarians

Cited by 100 publications

References 150 publications

Measuring functional brain recovery in regenerating planarians by assessing the behavioral response to the cholinergic compound cytisine

Measuring functional brain recovery in regenerating planarians by assessing the behavioral response to the cholinergic compound cytisine

Basics of Self-Regeneration

Planarian stem cells sense the identity of missing tissues to launch targeted regeneration

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