In preprints: cellular memory – the tension between old and new identities in the blastema DOI Open Access
Benjamin Tajer, Jessica L. Whited

Development, Journal Year: 2024, Volume and Issue: 151(1)

Published: Jan. 1, 2024

During salamander limb regeneration, a blastema – mass of progenitor cells forms at the site amputation. The proliferates, differentiates and is patterned to form regenerated tissues (McCusker et al., 2015) in process that has often been compared initial development limb. Indeed, there are many important molecular parallels between developmental bud; however, regeneration presents with unique challenges not present during development. development, bud follows consistent progression steps, emerging from predefined position specific time animal's Regeneration, by contrast, must restore missing structures, composition size which varies greatly injury as animal increases through growth 2015). Crucially, correctly establish its along proximodistal axis for precise replacement components. Further, orientation coordinates, such dorsoventral anterior-posterior axes, be properly specified regenerate appropriate structures correctly, largely achieved redeployment fibroblast factor (FGF), sonic hedgehog (SHH) bone morphogenetic protein (BMP) signaling gradients, but increasing evidence supports hypothesis population mature retains positional memory their migration into instructs patterning 2015; Otsuki Tanaka, 2021). Until recently, identity mechanisms cell remained mysterious.In preprint, colleagues make compelling case group Hand2-expressing dermal fibroblasts posterior may represent seat this axolotl (Ambystoma mexicanum) (Otsuki 2023 preprint). Hand2 transcription activates Shh expression zone posteriorizing activity (ZPA) then initiates regulatory cascade directs polarity developing (Charité 2000). Through transcriptomics several sophisticated reporter animals, demonstrate that, whereas gene fades shortly after maintains study uses inducible Cre reporters trace lineage expressed real-time express regeneration. authors find descended Shh-expressing ZPA do not, whole, major contribution regenerating In they see those later enriched regenerative ZPA.Having found give rise within ZPA, sought examine whether functionally required role, using CRISPR mutagenesis. 45% F0Hand2 CRISPants displayed defects were seen controls. These amplified 75% showing defects. mosaic knockout reduces degree disruption correlates severity both phenotypes. also tested ability CRISPant tissue accessory model (ALM). ALM, skin grafted an innervated wound anterior part limb; wild-type induces ectopic graft (Carlson, 1974; Endo 2004). does induce limb, suggesting activity. overexpressed Prrx1-promoter driven Hand2; Prrx1 throughout mesenchyme. F0 saw range phenotypes polydactyly formation limbs, indicating overexpression sufficient expression. Anterior animals strong induced limbs when transplanted weak did not. Together, these results suggest necessary regeneration.With likely carries memory, could reprogram They created Alx4-mCherry label Hand2-GFP tissue. Alx4-expressing When anterior, stopped expressing Alx4 began Shh, can reprogrammed Conversely, continued locations, once programmed, becomes fixed. performed similar experiments presence inhibition, agonists, finding expression, potentially enforcing fixed regeneration.Considering results, speculate specifies bud, initiating long-lasting small subpopulation cells. model, retain axolotl's life, allowing it recall events. Recent transcriptional lineage-tracing studies transition arguably some previous identities: although most origin, other contribute blastema. populations distinct identities entire process, giving same derived (Kragl 2009; Currie 2016; Choi 2017; Flowers Gerber 2018; Leigh 2018). combined recent findings colleagues, picture emerges have discrete aspects identities, despite undergoing drastic changes behavior, morphology Inevitably, reprogrammed, because no way fingers stubbornly elbow memories, and, arguably, profound preprint pertain reprogramming. cellular identity, more 'stubborn' than others, Alx4, identity. beautifully illustrate (in figure 5d), competence limited state. An obvious future direction circuitry perhaps interesting massively upregulates response injury, allows reprogramming Another our shows amputation triggers body-wide proliferation axolotls, priming creation (Payzin-Dogru 2023). As already primed would respond systemic signals provoked Ultimately, field will benefit we elucidate different origins descendent heed common call enter

Language: Английский

Hallmarks of regeneration DOI
Kenneth D. Poss, Elly M. Tanaka

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(9), P. 1244 - 1261

Published: Aug. 19, 2024

Language: Английский

Citations

10
Neural regulation of H3K27me3 during the induction of patterning competency in regenerating Axolotl limb cells DOI Creative Commons

Michael Raymond,

Matthew A. Cherubino, Warren A. Vieira

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 24, 2025

Language: Английский

Citations

0
Mechanisms of regeneration: to what extent do they recapitulate development? DOI Creative Commons
Can Aztekin

Development, Journal Year: 2024, Volume and Issue: 151(14)

Published: July 15, 2024

ABSTRACT One of the enduring debates in regeneration biology is degree to which mirrors development. Recent technical advances, such as single-cell transcriptomics and broad applicability CRISPR systems, coupled with new model organisms research, have led exploration this longstanding concept from a broader perspective. In Review, I outline historical parallels between development before focusing on recent research that highlights how dissecting divergence these processes can uncover previously unreported biological mechanisms. Finally, discuss advances position more dynamic variable process expanded possibilities for morphogenesis compared Collectively, insights into mechanisms orchestrate may reshape our understanding evolution regeneration, reveal hidden activated by injury, offer non-developmental strategies restoring lost or damaged organs tissues.

Language: Английский

Citations

3
Lineage tracing of Shh+ floor plate cells and dynamics of dorsal–ventral gene expression in the regenerating axolotl spinal cord DOI Creative Commons
Laura I. Arbanas, Emanuel Cura Costa, Osvaldo Chara

et al.

Development Growth & Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Both development and regeneration depend on signaling centers, which are sources of locally secreted tissue-patterning molecules. As many centers decommissioned before the end embryogenesis, a fundamental question is how can be re-induced later in life to promote after injury. Here, we use axolotl salamander model (Ambystoma mexicanum) address floor plate assembled for spinal cord regeneration. The an archetypal vertebrate center that secretes Shh ligand patterns neural progenitor cells during embryogenesis. Unlike mammals, axolotls continue express genes (including Shh) downstream dorsal-ventral patterning their throughout life, including at steady state. parsimonious hypothesis Shh+ give rise functional had not been tested. Using HCR situ hybridization mathematical modeling, first quantified behaviors domains, identifying significant increases gene expression level size Next, established transgenic specifically label fate map vivo. We found labeled gave plate, other tail amputation. Thus, despite changes domain expression, retain identity regeneration, acting as stable cellular source this cord.

Language: Английский

Citations

2
Making a new limb out of old cells: Exploring endogenous cell reprogramming and its role during limb regeneration DOI

Michael J. Raymond,

Catherine McCusker

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 326(2), P. C505 - C512

Published: Dec. 18, 2023

Cellular reprogramming is characterized by the induced dedifferentiation of mature cells into a more plastic and potent state. This process can occur through artificial manipulations in laboratory such as nuclear pluripotent stem cell (iPSC) generation, endogenously vivo during amphibian limb regeneration. In amphibians Mexican axolotl, regeneration permissive environment formed nerve-dependent signaling wounded tissue. When exposed to these signals, connective tissue dedifferentiate progenitor-like state allows acquire new pattern information, property called positional plasticity. Here, we review our current understanding endogenous why it important for successful We will also explore how naturally plasticity were leveraged study missing established regenerating

Language: Английский

Citations

4
Lineage tracing ofShh+floor plate cells and dynamics of dorsal-ventral gene expression in the regenerating axolotl spinal cord DOI Creative Commons
Laura I. Arbanas, Emanuel Cura Costa, Osvaldo Chara

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Abstract Both development and regeneration depend on signalling centres, which are sources of locally secreted tissue-patterning molecules. As many centres decommissioned before the end embryogenesis, a fundamental question is how can be re-induced later in life to promote after injury. Here, we use axolotl salamander model ( Ambystoma mexicanum ) address floor plate assembled for spinal cord regeneration. The an archetypal vertebrate centre that secretes Shh ligand patterns neural progenitor cells during embryogenesis. Unlike mammals, axolotls continue express genes (including downstream dorsal-ventral patterning their throughout life, including at steady state. parsimonious hypothesis + give rise functional had not been tested. Using HCR situ hybridisation mathematical modelling, first quantitated behaviours domains, identifying significant increases gene expression level size Next, established transgenic specifically label fate map vivo . We found labelled Shh+ gave plate, other tail amputation. Thus, despite changes domain expression, retain identity regeneration, acting as stable cellular source this cord.

Language: Английский

Citations

1
In preprints: cellular memory – the tension between old and new identities in the blastema DOI Open Access
Benjamin Tajer, Jessica L. Whited

Development, Journal Year: 2024, Volume and Issue: 151(1)

Published: Jan. 1, 2024

During salamander limb regeneration, a blastema – mass of progenitor cells forms at the site amputation. The proliferates, differentiates and is patterned to form regenerated tissues (McCusker et al., 2015) in process that has often been compared initial development limb. Indeed, there are many important molecular parallels between developmental bud; however, regeneration presents with unique challenges not present during development. development, bud follows consistent progression steps, emerging from predefined position specific time animal's Regeneration, by contrast, must restore missing structures, composition size which varies greatly injury as animal increases through growth 2015). Crucially, correctly establish its along proximodistal axis for precise replacement components. Further, orientation coordinates, such dorsoventral anterior-posterior axes, be properly specified regenerate appropriate structures correctly, largely achieved redeployment fibroblast factor (FGF), sonic hedgehog (SHH) bone morphogenetic protein (BMP) signaling gradients, but increasing evidence supports hypothesis population mature retains positional memory their migration into instructs patterning 2015; Otsuki Tanaka, 2021). Until recently, identity mechanisms cell remained mysterious.In preprint, colleagues make compelling case group Hand2-expressing dermal fibroblasts posterior may represent seat this axolotl (Ambystoma mexicanum) (Otsuki 2023 preprint). Hand2 transcription activates Shh expression zone posteriorizing activity (ZPA) then initiates regulatory cascade directs polarity developing (Charité 2000). Through transcriptomics several sophisticated reporter animals, demonstrate that, whereas gene fades shortly after maintains study uses inducible Cre reporters trace lineage expressed real-time express regeneration. authors find descended Shh-expressing ZPA do not, whole, major contribution regenerating In they see those later enriched regenerative ZPA.Having found give rise within ZPA, sought examine whether functionally required role, using CRISPR mutagenesis. 45% F0Hand2 CRISPants displayed defects were seen controls. These amplified 75% showing defects. mosaic knockout reduces degree disruption correlates severity both phenotypes. also tested ability CRISPant tissue accessory model (ALM). ALM, skin grafted an innervated wound anterior part limb; wild-type induces ectopic graft (Carlson, 1974; Endo 2004). does induce limb, suggesting activity. overexpressed Prrx1-promoter driven Hand2; Prrx1 throughout mesenchyme. F0 saw range phenotypes polydactyly formation limbs, indicating overexpression sufficient expression. Anterior animals strong induced limbs when transplanted weak did not. Together, these results suggest necessary regeneration.With likely carries memory, could reprogram They created Alx4-mCherry label Hand2-GFP tissue. Alx4-expressing When anterior, stopped expressing Alx4 began Shh, can reprogrammed Conversely, continued locations, once programmed, becomes fixed. performed similar experiments presence inhibition, agonists, finding expression, potentially enforcing fixed regeneration.Considering results, speculate specifies bud, initiating long-lasting small subpopulation cells. model, retain axolotl's life, allowing it recall events. Recent transcriptional lineage-tracing studies transition arguably some previous identities: although most origin, other contribute blastema. populations distinct identities entire process, giving same derived (Kragl 2009; Currie 2016; Choi 2017; Flowers Gerber 2018; Leigh 2018). combined recent findings colleagues, picture emerges have discrete aspects identities, despite undergoing drastic changes behavior, morphology Inevitably, reprogrammed, because no way fingers stubbornly elbow memories, and, arguably, profound preprint pertain reprogramming. cellular identity, more 'stubborn' than others, Alx4, identity. beautifully illustrate (in figure 5d), competence limited state. An obvious future direction circuitry perhaps interesting massively upregulates response injury, allows reprogramming Another our shows amputation triggers body-wide proliferation axolotls, priming creation (Payzin-Dogru 2023). As already primed would respond systemic signals provoked Ultimately, field will benefit we elucidate different origins descendent heed common call enter

Language: Английский

Citations

0