TOR signaling regulates planarian stem cells and controls localized and organismal growth

Peiris, T. Harshani; Weckerle, Frank; Ozamoto, Elyse; Ramirez, Daniel M. Carter; Davidian, Devon; García‐Ojeda, Marcos E.; Oviedo, Néstor J.

doi:10.1242/dev.084178

Cited by 5 publications

(9 citation statements)

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“…The TOR signal is an evolutionary conserved pathway that integrates nutrient status with cell growth and division (Loewith et al, 2011). Although its role in relation to the nutritional status of planarians has not been uncovered, its inhibition in regenerating planarians leads to the inability to form blastemas and to remodel the pre-existing tissues (Peiris et al, 2012, Tu et al, 2012. The inhibition of PTEN and smg-1 in planarians produces overproliferation and outgrowths that are rescued by Rapamycin, a TOR pathway inhibitor (Oviedo et al, 2008;González-Estévez et al, 2012).…”

Section: Size Control and Organ Proportionalitymentioning

confidence: 99%

Rebuilding a planarian: from early signaling to final shape

Cebrià¹,

Adell²,

Saló³

2018

Int. J. Dev. Biol.

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Why some animals can regenerate and others not has fascinated biologists since the first examples of regeneration were reported. Although many animal phyla include species with some regenerative ability, mainly restricted to particular cell types or tissues, there are some other species capable of regenerating complex structures, such as the vertebrate limb and heart. More remarkably, there are some examples of animals that can regenerate the whole body from a tiny piece of them. Understanding how regeneration is triggered and achieved in these animals is fundamental not only to understand this fascinating primary biological question, but also because of its implications for the field of regenerative medicine. Here, we discuss one of the models with higher regenerative capabilities: the freshwater planarians. Two key features make planarians an attractive model to study regeneration: the presence of adult pluripotent stem cells and the permanent activation of the morphogenetic mechanisms that instruct cell fate. Here, we revise our current knowledge of key events that lead to successful regeneration including: how heterogeneous is the stem cell population; what are the immediate changes at the gene level after amputation and what triggers the regenerative response; how is axial polarity re-established; how do the different cell types differentiate from lineage-committed progenitors and how is size and organ proportionality controlled. Finally, we point out some open questions that the field needs to address in the near future.

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Section: Size Control and Organ Proportionalitymentioning

confidence: 99%

Rebuilding a planarian: from early signaling to final shape

Cebrià¹,

Adell²,

Saló³

2018

Int. J. Dev. Biol.

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“…Mechanistically, TOR exerts its functions as the catalytic subunit of two distinct complexes, TORC1 and TORC2, via interaction with the Raptor and Rictor accessory proteins, respectively (Wullschleger et al , 2006). Previous work in planarians has shown that the role of TOR in regeneration is carried out specifically through TORC1 (Tu et al , 2012; Peiris et al , 2012). Indeed, we observed significant growth of RNA low neoblasts in both control(RNAi) and rictor(RNAi) animals at 48 hpa, but not in raptor(RNAi) animals (Fig 5E).…”

Section: Resultsmentioning

confidence: 99%

“…Following amputation, the neoblast population exhibits a robust proliferative response characterized by two peaks in mitosis at 6‐ and 48‐h post‐amputation (hpa) (Wenemoser & Reddien, 2010). This mitotic response is dependent on TOR (target of rapamycin) signalling through TOR complex 1 (TORC1), which is required for regeneration (Wenemoser & Reddien, 2010; Peiris et al , 2012; Tu et al , 2012). Although TOR is known to be involved in controlling the rate of proliferation of neoblasts during regeneration, the mechanism of this control is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Identification of TOR‐responsive slow‐cycling neoblasts in planarians

2021

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Epimorphic regeneration commonly relies on the activation of reserved stem cells to drive new cell production. The planarian Schmidtea mediterranea is among the best regenerators in nature, thanks to its large population of adult stem cells, called neoblasts. While neoblasts have long been known to drive regeneration, whether a subset of neoblasts is reserved for this purpose is unknown. Here, we revisit the idea of reserved neoblasts by approaching neoblast heterogeneity from a regulatory perspective. By implementing a new fluorescence‐activated cell sorting strategy in planarians, we identify a population of neoblasts defined by low transcriptional activity. These RNAlow neoblasts are relatively slow‐cycling at homeostasis and undergo a morphological regeneration response characterized by cell growth at 48 h post‐amputation. At this time, RNAlow neoblasts proliferate in a TOR‐dependent manner. Additionally, knockdown of the tumour suppressor Lrig‐1, which is enriched in RNAlow neoblasts, results in RNAlow neoblast growth and hyperproliferation at homeostasis, and ultimately delays regeneration. We propose that slow‐cycling RNAlow neoblasts represent a regeneration‐reserved neoblast population.

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“…Two systemic peaks of neoblast division occur at six and 24 hpi without visible signs of host tissue damage. This is intriguing because physiological increases in neoblast division generally occur via metabolic inputs such as nutrient availability through feeding or in response to tissue injury (Peiris et al, 2012; Saló and Baguñà, 1984; Wenemoser and Reddien, 2010).…”

Section: Discussionmentioning

confidence: 99%

Epithelial Infection with Candida albicans Elicits a Multi-system Response in Planarians

Maciel

Valle-Arevalo

Ziman

et al. 2020

Preprint

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Candida albicans is one of the most common fungal pathogens of humans. Prior work introduced the planarian Schmidtea mediterranea as a new model system to study the host response to fungal infection at the organismal level. In the current study, we analyzed host-pathogen changes that occurred in situ during early infection with C. albicans. We found that the transcription factor Bcr1 and its downstream adhesin Als3 are required for C. albicans to adhere to and colonize the planarian epithelial surface, and that adherence of C. albicans triggers a multi-system host response that is mediated by the Dectin signaling pathway. This infection response is characterized by two peaks of stem cell divisions and transcriptional changes in differentiated tissues including the nervous and the excretory systems. This response bears some resemblance to a wound-like response to physical injury; however, it takes place without visible tissue damage and it engages a distinct set of progenitor cells. Overall, we identified two C. albicans proteins that mediate epithelial infection of planarians and a comprehensive host response facilitated by diverse tissues to effectively clear the infection.

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TOR signaling regulates planarian stem cells and controls localized and organismal growth

Cited by 5 publications

References 1 publication

Rebuilding a planarian: from early signaling to final shape

Rebuilding a planarian: from early signaling to final shape

Identification of TOR‐responsive slow‐cycling neoblasts in planarians

Epithelial Infection with Candida albicans Elicits a Multi-system Response in Planarians

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