Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea

Barberán, Sara; Martín-Durán, José M.; Cebrià, Francesc

doi:10.1038/srep28071

Cited by 35 publications

(33 citation statements)

References 61 publications

(109 reference statements)

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“…These results strongly suggest that Smed-egfr-1 is not required for the specification of gut progenitors but is required for their differentiation into mature phagocytes and goblet cells (Barberán et al, 2016a). In this same study, the authors identified a putative ligand of Smed-egfr-1 named Smed-nrg-1, which shares homology with neuregulin-type EGF ligands (Barberán et al, 2016b). The silencing of Smed-nrg-1 phenocopies the defects observed after knockdown of Smed-egfr-1, supporting the hypothesis that Smed-nrg-1 may act as a ligand of Smed-egfr-1 in vivo, thereby regulating the differentiation of gut progenitors.…”

Section: Gut Cellsmentioning

confidence: 94%

“…A recent study demonstrated a key role of the epidermal growth factor receptor (EGFR) signaling pathway in the differentiation of gut progenitors during regeneration and homeostasis (Barberán et al, 2016a). Smed-egfr-1 is one of several planarian homologues of the EGFR family of tyrosine kinase receptors (Barberán et al, 2016b) and is expressed in differentiated gut cells and in gut progenitors in the mesenchyme around the gut branches (Barberán et al, 2016a). Whereas Smed-egfr-1 silencing inhibits the differentiation of new gut cells, as demonstrated in EdU incorporation experiments, the number of gut progenitors defined by co-expression of hnf-4/SMEDWI-1 and gata4/5/6/SMEDWI-1 increases significantly.…”

Section: Gut Cellsmentioning

confidence: 99%

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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: Gut Cellsmentioning

confidence: 94%

Section: Gut Cellsmentioning

confidence: 99%

Rebuilding a planarian: from early signaling to final shape

Cebrià¹,

Adell²,

Saló³

2018

Int. J. Dev. Biol.

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“…Nevertheless, some potential factors or downstream effectors have been identified from RNAi screens. The epidermal growth factor receptor (EGFR) signaling pathway is crucial for neoblast regulation and cell fate specification . Smed‐egfr‐3 RNAi inhibits blastema formation and impairs cellular differentiation because of a dysregulation in asymmetric cell division .…”

Section: Molecular Mechanisms Underlying Nervous System Regenerationmentioning

confidence: 99%

“…The epidermal growth factor receptor (EGFR) signaling pathway is crucial for neoblast regulation and cell fate specification. [101][102][103] Smed-egfr-3 RNAi inhibits blastema formation and impairs cellular differentiation because of a dysregulation in asymmetric cell division. 101,103 Smed-egr-4, a putative downstream target of Smed-egfr-3, is primarily expressed in the brain and is required for brain regeneration; when Smed-egr-4 is knocked down, planarians reestablish anterior polarity, but fail to induce neural specification or form a brain primordium.…”

Section: Signaling Factors Involved In Brain Inductionmentioning

confidence: 99%

Nervous system development and regeneration in freshwater planarians

Ross

Currie

Pearson

et al. 2017

WIREs Developmental Biology

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Planarians have a long history in the fields of developmental and regenerative biology. These animals have also sparked interest in neuroscience due to their neuroanatomy, spectrum of simple behaviors, and especially, their almost unparalleled ability to generate new neurons after any type of injury. Research in adult planarians has revealed that neuronal subtypes homologous to those found in vertebrates are generated from stem cells throughout their lives. This feat is recapitulated after head amputation, wherein animals are capable of regenerating whole brains and regaining complete neural function. In this review, we summarize early studies on the anatomy and function of the planarian nervous system and discuss our present knowledge of the molecular mechanisms governing neurogenesis in planarians. Modern studies demonstrate that the transcriptional programs underlying neuronal specification are conserved in these remarkable organisms. Thus, planarians are outstanding models to investigate questions about how stem cells can replace neurons in vivo. WIREs Dev Biol 2017, 6:e266. doi: 10.1002/wdev.266 For further resources related to this article, please visit the WIREs website.

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“…Therefore, Smed--egfr--1 appears to be necessary not for the specification of the gut progenitors but for their final differentiation (Barberán et al, 2016a). In planarians, the EGFR family has been expanded and 6 homologues have been identified in the model species Schmidtea mediterranea (Barberán et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

Smed-egfr-4 is required for planarian eye regeneration

Elena

Pallarès

Romero

et al. 2018

Preprint

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Short running title: egfr--4 in eye regeneration ABSTRACTPlanarians are amazing animals that can regenerate a whole body from a tiny piece of them thanks to their pluripotent stem cells, the neoblasts. Planarian neoblasts include both pluripotent stem cells and specialized lineage--committed progenitors that give rise to all the mature cell types during regeneration and homeostatic cell turnover in these plastic animals. Little is known, however, about the mechanisms that regulate neoblast differentiation. Recently, it has been shown that Smed--egfr--1, a homologue of the epidermal growth factor receptor (EGFR) family is required for the final differentiation of the gut progenitors into mature cells but not for their specification.As planarians have several EGFR homologues it has been proposed that they could have diverged functionally to regulate the differentiation of the different cell types found in these animals. Here, we report on the function of Smed--egfr--4 on eye regeneration. The silencing of this gene by RNAi results in animals regenerating smaller eyes compared to controls. The numbers of both eye mature cell types, photoreceptor neurons and eye--cup pigment cells, are significantly decreased in the Smed--egfr--4(RNAi) animals. In contrast, the number of eye progenitor cells expressing the specific markers Smed--ovo and Smed--sp6--9 is increased. These results suggest that Smed--egfr--4 would be required not for the specification of eye progenitor cells but rather for their final differentiation and support the idea that in planarians the EGFR pathway could play a general role regulating the differentiation of lineage--committed progenitors.

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Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea

Cited by 35 publications

References 61 publications

Rebuilding a planarian: from early signaling to final shape

Rebuilding a planarian: from early signaling to final shape

Nervous system development and regeneration in freshwater planarians

Smed-egfr-4 is required for planarian eye regeneration

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