Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

Adler, Carolyn E.; Seidel, Chris; McKinney, Sean A.; Alvarado, Alejandro Sánchez

doi:10.7554/elife.02238

Cited by 136 publications

(179 citation statements)

References 81 publications

(118 reference statements)

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“…S8A-D). Analysis of the expression of the pharynx-progenitor marker foxA (Adler et al, 2014) showed no significant differences between treated animals and controls (Fig. S8E,F).…”

Section: Egfr-1 Silencing Increases the Number Of Gut Progenitor Cellsmentioning

confidence: 99%

“…Neoblasts are the only dividing cells of planarians (Morita and Best, 1984;Newmark and Sánchez Alvarado, 2000) and thus can differentiate into any cell type. Accordingly, the neoblast population consists of a compartment of pluripotent ASCs (Wagner et al, 2011) and a heterogeneous pool of lineage-restricted progenitors (Hayashi et al, 2010;Moritz et al, 2012;Reddien, 2013;Scimone et al, 2014;van Wolfswinkel et al, 2014), which can be distinguished by the expression of tissue-specific transcription factors (Adler et al, 2014;Cowles et al, 2013;Lapan and Reddien, 2012;Scimone et al, 2014Scimone et al, , 2011Wagner et al, 2011). Despite recent advances, the genes and molecular pathways that regulate the differentiation of known progenitors into distinct mature cell types remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

2016

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The planarian Schmidtea mediterranea maintains and regenerates all its adult tissues through the proliferation and differentiation of a single population of pluripotent adult stem cells (ASCs) called neoblasts. Despite recent advances, the mechanisms regulating ASC differentiation into mature cell types are poorly understood. Here, we show that silencing of the planarian EGF receptor egfr-1 by RNA interference (RNAi) impairs gut progenitor differentiation into mature cells, compromising gut regeneration and maintenance. We identify a new putative EGF ligand, nrg-1, the silencing of which phenocopies the defects observed in egfr-1(RNAi) animals. These findings indicate that egfr-1 and nrg-1 promote gut progenitor differentiation, and are thus essential for normal cell turnover and regeneration in the planarian gut. Our study demonstrates that the EGFR signaling pathway is an important regulator of ASC differentiation in planarians.

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“…S8A-D). Analysis of the expression of the pharynx-progenitor marker foxA (Adler et al, 2014) showed no significant differences between treated animals and controls (Fig. S8E,F).…”

Section: Egfr-1 Silencing Increases the Number Of Gut Progenitor Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

2016

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“…Neoblasts are a heterogeneous population that includes both pluripotent cells and distinct subpopulations specified for production of multiple differentiated tissues (Adler et al, 2014;Cowles et al, 2013;Currie and Pearson, 2013;Forsthoefel et al, 2012;Lapan and Reddien, 2012;Marz et al, 2013;Scimone et al, 2011Scimone et al, , 2014avan Wolfswinkel et al, 2014;Vásquez-Doorman and Petersen, 2014;Vogg et al, 2014;Wenemoser et al, 2012). We hypothesized that notum and wnt11-6 might regulate brain cell production by controlling numbers of brain cell progenitors marked by expression of lineage-specific transcription factors.…”

Section: Planarians Robustly Restore Brain:body Proportionality Throumentioning

confidence: 99%

“…Growth from feeding or epimorphic regeneration depends on parenchymal cells termed neoblasts that are the only proliferating cells in adult planarians (Baguñà, 1976;Newmark and Sánchez Alvarado, 2000;Reddien et al, 2005b). Neoblasts are a heterogeneous population containing both adult pluripotent stem cells (Wagner et al, 2011) and more lineage-restricted dividing cells (Adler et al, 2014;Cowles et al, 2013;Currie and Pearson, 2013;Forsthoefel et al, 2012;Lapan and Reddien, 2012;Marz et al, 2013;Scimone et al, 2014aScimone et al, ,b, 2011van Wolfswinkel et al, 2014;Vásquez-Doorman and Petersen, 2014;Vogg et al, 2014;Wenemoser et al, 2012). Tissue removal results in proliferative activation of neoblasts thought to be necessary for production of missing tissue types within the regeneration blastema.…”

Section: Introductionmentioning

confidence: 99%

Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain

2015

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Mechanisms determining final organ size are poorly understood. Animals undergoing regeneration or ongoing adult growth are likely to require sustained and robust mechanisms to achieve and maintain appropriate sizes. Planarians, well known for their ability to undergo whole-body regeneration using pluripotent adult stem cells of the neoblast population, can reversibly scale body size over an order of magnitude by controlling cell number. Using quantitative analysis, we showed that after injury planarians perfectly restored brain:body proportion by increasing brain cell number through epimorphosis or decreasing brain cell number through tissue remodeling (morphallaxis), as appropriate. We identified a pathway controlling a brain size set-point that involves feedback inhibition between wnt11-6/wntA/wnt4a and notum, encoding conserved antagonistic signaling factors expressed at opposite brain poles. wnt11-6/wntA/wnt4a undergoes feedback inhibition through canonical Wnt signaling but is likely to regulate brain size in a non-canonical pathway independently of beta-catenin-1 and APC. Wnt/Notum signaling tunes numbers of differentiated brain cells in regenerative growth and tissue remodeling by influencing the abundance of brain progenitors descended from pluripotent stem cells, as opposed to regulating cell death. These results suggest that the attainment of final organ size might be accomplished by achieving a balance of positional signaling inputs that regulate the rates of tissue production.

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“…2012; Elliott & Sánchez Alvarado 2013; Adler et al. 2014; Scimone et al. 2014; van Wolfswinkel et al.…”

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The NuRD complex componentp66suppresses photoreceptor neuron regeneration in planarians

Vásquez-Doorman

Petersen

2016

Regeneration

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Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin‐modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA‐binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians. This suppressive effect appeared restricted to PRNs because p66 inhibition did not influence numbers of eye pigment cup cells (PCCs) and decreased numbers of brain neurons and epidermal progenitors. PRNs from p66(RNAi) animals differentiated with some abnormalities but nonetheless produced arrestin+ projections to the brain. p66 inhibition produced excess ovo+otxA+ PRN progenitors without affecting numbers of ovo+otxA− PCC progenitors, and ovo and otxA were each required for the p66(RNAi) excess PRN phenotype. Together these results suggest that p66 acts through the NuRD complex to suppress PRN production by limiting expression of lineage‐specific transcription factors.

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Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

Cited by 136 publications

References 81 publications

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain

The NuRD complex componentp66suppresses photoreceptor neuron regeneration in planarians

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