Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration

Seminars in Cell and Developmental Biology, Год журнала: 2025, Номер 170, С. 103610 - 103610

Опубликована: Апрель 10, 2025

Язык: Английский

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Injury-Induced Neuregulin-Erbb Signaling from Muscle Mobilizes Stem Cells for Whole-Body Regeneration in Acoels

Опубликована: Янв. 1, 2025

The activation of progenitor cells near wound sites is a common feature regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body are still incompletely understood. acoel Hofstenia miamia undergoes using Piwi+ pluripotent adult stem (neoblasts) that accumulate at amputation early process. EGFR pathway has broad roles controlling proliferation, migration, differentiation, and cell survival metazoans. Using candidate RNAi screening approach, we identify erbB4-2 Neuregulin nrg-1 genesas essential blastema formation. Structure prediction NRG-1 ERBB4-2 proteins supports likelihood these factors interacting directly. After injuries, expression induced body-wall muscle site by 6 hours localizes to tip outgrowing over next several days, while broadly expressed, including neoblasts. Under nrg-1(RNAi) erbB4-2(RNAi) conditions impair formation, animals undergo earliest responses injury activate Early Growth Response transcription factor egr, indicating crucial role downstream initial activation. possess H3P+ mitotic neoblasts which hyperproliferate normally after amputation, fail site. Therefore, provides source Neuregulin-ErbB necessary mobilization proliferative progenitors enable outgrowth Hofstenia. These results indicate shared functional requirement between planarians acoels 550 million years evolution.

Язык: Английский

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Autophagy in Tissue Repair and Regeneration

Cells, Год журнала: 2025, Номер 14(4), С. 282 - 282

Опубликована: Фев. 14, 2025

Autophagy is a cellular recycling system that, through the sequestration and degradation of intracellular components regulates multiple functions to maintain homeostasis survival. Dysregulation autophagy closely associated with development physiological alterations human diseases, including loss regenerative capacity. Tissue regeneration highly complex process that relies on coordinated interplay several processes, such as injury sensing, defense responses, cell proliferation, differentiation, migration, senescence. These processes act synergistically repair or replace damaged tissues restore their morphology function. In this review, we examine evidence supporting involvement pathway in different mechanisms comprising across contexts. Additionally, explore how modulating can enhance accelerate repair, highlighting promising therapeutic target medicine for autophagy-based treatments diseases.

Язык: Английский

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Multifaceted conserved functions of Notch during post-embryonic neurogenesis in the annelidPlatynereis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

ABSTRACT Notch signaling is an evolutionarily conserved pathway known to orchestrate neurogenesis by regulating the transition of progenitor cells differentiated neurons and glia, as well directing neurite outgrowth axon guidance in many species. Although extensively studied vertebrates ecdysozoans, role spiralians (including mollusks, annelids or flatworms) remains largely unexplored, limiting our understanding its functions across bilaterians. In this study, we focus on segmented annelid Platynereis dumerilii , a model organism neurobiology regeneration, investigate during post-embryonic developmental processes. We show that components are expressed neurogenic territories both posterior elongation two processes requiring sustained neurogenesis. Through chemical inhibitions RNA-seq profiling, demonstrate regulates neural specification, differentiation, overall balance regenerating elongating part. Moreover, disruption activity leads severe defects pygidial central nervous system organization, including abnormal impaired outgrowth. Altogether, results support hypothesis has multifaceted bilaterians, shedding light ancestral critical pathway.

Язык: Английский

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A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient

Опубликована: Март 13, 2025

Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Язык: Английский

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A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient

Опубликована: Март 13, 2025

Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Язык: Английский

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A genetic and microscopy toolkit for manipulating and monitoring regeneration in Macrostomum lignano

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114892 - 114892

Опубликована: Окт. 19, 2024

Язык: Английский

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A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Summary Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Язык: Английский

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Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

Why mammals cannot regenerate limbs, unlike amphibians, presents a longstanding puzzle in biology. We show that exposing ex vivo amputated embryonic mouse limbs to subatmospheric oxygen environment, or stabilizing oxygen-sensitive HIF1A enables not only rapid wound healing, but alters cellular mechanics, and reshapes the histone landscape prime regenerative fates. Conversely, Xenopus tadpole display low oxygen-sensing capacity, robust landscape, glycolytic programs even under high oxygen. This reduced stark contrast mammals, associates with decreased HIF1A-regulating gene expressions. Our findings thus uncover species-specific sensing as unifying mechanism for limb regeneration initiation across vertebrates, reveal how aquatic habitats may enhance capabilities, identify targetable barriers unlock latent adult mammals.

Язык: Английский

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Injury-induced Neuregulin-ErbB signaling from muscle mobilizes stem cells for whole-body regeneration in Acoels

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 23, 2024

The activation of progenitor cells near wound sites is a common feature regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body are still incompletely understood. acoel Hofstenia miamia undergoes using Piwi+ pluripotent adult stem (neoblasts) that accumulate at amputation early process. EGFR pathway has broad roles controlling proliferation, migration, differentiation, and cell survival metazoans. Using candidate RNAi screening approach, we identify erbB4-2 Neuregulin nrg-1 genes as essential blastema formation. Structure prediction NRG-1 ERBB4-2 proteins supports likelihood these factors interacting directly. After injuries, expression induced body-wall muscle site by 6 hours localizes to tip outgrowing over next several days, while broadly expressed, including neoblasts. Under nrg-1(RNAi) erbB4-2(RNAi) conditions impair formation, animals undergo earliest responses injury activate Early Growth Response transcription factor egr, indicating crucial role downstream initial activation. possess H3P+ mitotic neoblasts which hyperproliferate normally after amputation, fail site. Therefore, provides source Neuregulin-ErbB necessary mobilization proliferative progenitors enable outgrowth Hofstenia. These results indicate shared functional requirement between planarians acoels 550 million years evolution.

Язык: Английский

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