Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

Farkas, Johanna E; Freitas, Polina D.; Bryant, Donald M.; Whited, Jessica L.; Monaghan, James R.

doi:10.1242/dev.133363

Cited by 97 publications

(95 citation statements)

References 48 publications

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“…A more detailed study of neuregulin 1 (NRG1) in regenerating axolotl limbs (Farkas, Freitas, Bryant, Whited, & Monaghan, 2016) showed that transcripts of nrg1 and its receptors erbb2 and erbb3 are expressed by the basal cells of the AEC and by 56% of the blastema mesenchyme cells. Antibody staining revealed expression of NRG1 and ErbB2 in dorsal root ganglia and peripheral limb nerves.…”

Section: Blastema Growthmentioning

confidence: 99%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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This review explores the historical and current state of our knowledge about urodele limb regeneration. Topics discussed are (1) blastema formation by the proteolytic histolysis of limb tissues to release resident stem cells and mononucleate cells that undergo dedifferentiation, cell cycle entry and accumulation under the apical epidermal cap. (2) The origin, phenotypic memory, and positional memory of blastema cells. (3) The role played by macrophages in the early events of regeneration. (4) The role of neural and AEC factors and interaction between blastema cells in mitosis and distalization. (5) Models of pattern formation based on the results of axial reversal experiments, experiments on the regeneration of half and double half limbs, and experiments using retinoic acid to alter positional identity of blastema cells. (6) Possible mechanisms of distalization during normal and intercalary regeneration. (7) Is pattern formation is a self‐organizing property of the blastema or dictated by chemical signals from adjacent tissues? (8) What is the future for regenerating a human limb?

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Section: Blastema Growthmentioning

confidence: 99%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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“…[7][8][9][10] Substitute molecules for nerve functions in blastema induction have been tested for, and some candidate genes have been described. 6,[11][12][13][14][15] Recently, a brand-new experimental system called the accessory limb model (ALM) proposed the nerve molecules that can induce regeneration in multiple organs and species. 13,14,[16][17][18][19][20] The ALM is a better experimental design for the investigation of nerve functions in limb regeneration.…”

Section: Introductionmentioning

confidence: 99%

Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum

Iwata

Makanae

Satoh

2019

Developmental Dynamics

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Background Urodele amphibians are capable of regenerating their organs after severe damage. During such regeneration, participating cells are given differentiation instructions by the surrounding cells. Limb regeneration has been investigated as a representative phenomenon of organ regeneration. Cells known as blastema cells are induced after limb amputation. In this process, dermal fibroblasts are dedifferentiated and become undifferentiated similar to limb bud cells. Just like limb bud cells, the induced blastema cells are positioned along the three limb developmental axes: the dorsoventral, the anteroposterior, and the proximodistal. The accurate developmental axes are essential for reforming the structures correctly. Despite the importance of the developmental axes, the relationship between the newly establishing developmental axes and existing limb axes was not well described with molecular markers. Results In this study, we grafted skin from GFP‐transgenic axolotls and traced the cell lineage with position‐specific gene expressions in order to investigate the correlation of the newly established axes and cellular origin. Shh‐ and Lmx1b‐expressing cells emerged from the posterior skin and dorsal skin, respectively, even though the skin was transplanted to an inconsistent position. Shox2, a posterior marker gene, could be activated in cells derived from distal skin. Conclusions Our results suggest that the location memories on anteroposterior and dorsoventral axes are relatively stable in a regenerating blastema though cellular differentiation is reprogrammed.

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“…In addition, neurons or macrophages can act as sources of GFs at the wound site (Brockes & Kintner, ; Lu et al, ; L. Wang, Marchionni, & Tassava, ). In many of these instances (mammalian bone and cartilage (Kempen et al, ), blood vessels (Gasparini, Burighel, Manni, & Zaniolo, ; Koch & Claesson‐Welsh, ), heart (Uva et al, ; Wadugu & Kuhn, ), and liver (Mao, Glorioso, & Scott, ), amphibian lens (Henry, Thomas, Hamilton, Moore, & Perry, ) and limb (Brockes & Kintner, ; Farkas, Freitas, Bryant, Whited, & Monaghan, ; Satoh, Mitogawa, & Makanae, ), and zebrafish heart and fin regeneration (Kim et al, ; Lee, Grill, Sanchez, Murphy‐Ryan, & Poss, ; Poss et al, )), functional studies have revealed that GFs or the pathways activated by GF receptors, regulate proliferation (as either activators or inhibitors) (summarized in Figure ).…”

Section: Wound Signaling and The Regulation Of Proliferationmentioning

confidence: 99%

Wound‐induced cell proliferation during animal regeneration

Ricci

Srivastava

2018

WIREs Developmental Biology

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Many animal species are capable of replacing missing tissues that are lost upon injury or amputation through the process of regeneration. Although the extent of regeneration is variable across animals, that is, some animals can regenerate any missing cell type whereas some can only regenerate certain organs or tissues, regulated cell proliferation underlies the formation of new tissues in most systems. Notably, many species display an increase in proliferation within hours or days upon wounding. While different cell types proliferate in response to wounding in various animal taxa, comparative molecular data are beginning to point to shared wound-induced mechanisms that regulate cell division during regeneration. Here, we synthesize current insights about early molecular pathways of regeneration from diverse model and emerging systems by considering these species in their evolutionary contexts. Despite the great diversity of mechanisms underlying injury-induced cell proliferation across animals, and sometimes even in the same species, similar pathways for proliferation have been implicated in distantly related species (e.g., small diffusible molecules, signaling from apoptotic cells, growth factor signaling, mTOR and Hippo signaling, and Wnt and Bmp pathways). Studies that explicitly interrogate molecular and cellular regenerative mechanisms in understudied animal phyla will reveal the extent to which early pathways in the process of regeneration are conserved or independently evolved. This article is categorized under: Comparative Development and Evolution > Body Plan Evolution Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Comparative Development and Evolution > Model Systems.

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Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

Cited by 97 publications

References 48 publications

Mechanisms of urodele limb regeneration

Mechanisms of urodele limb regeneration

Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum

Wound‐induced cell proliferation during animal regeneration

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