Overexpression of the transcription factor Msx1 is insufficient to drive complete regeneration of refractory stage <i>Xenopus laevis</i> hindlimbs

Barker, Donna; Beck, Caroline W.

doi:10.1002/dvdy.21923

Cited by 22 publications

(17 citation statements)

References 55 publications

(89 reference statements)

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“…Our data show that as regeneration proceeds, a pool of fast-cycling cells persists at the distal tip of the fin, characterized by expression of msxe and aldh1a2 and strong msxb expression. RA maintains this blastema region by enhancing expression of the pro-survival gene bcl2 (Blum and Begemann, 2012), whereas Msx homologs are important regulators of de-differentiation in several regenerating structures, such as the mouse digit tip (Han et al, 2003) and Xenopus and Amphioxus tails (Barker and Beck, 2009;Somorjai et al, 2012 is reversed when Notch induction is stopped, indicating that Notch maintains an undifferentiated, proliferative state of blastema cells by promoting msxb, msxe and aldh1a2 expression.…”

Section: Discussionmentioning

confidence: 99%

“…By 2 days post amputation (2 dpa), a blastema consisting of undifferentiated, highly proliferative cells has formed beneath the wound epidermis distal to each amputated fin ray. These cells express the Msx homeobox family members msxb and msxe, which label undifferentiated/progenitor-like cells in a variety of regenerating tissues (Akimenko et al, 1995;Han et al, 2003;Barker and Beck, 2009;Yoshinari et al, 2009). In the third phase, differentiating blastema cells progressively reconstitute the lost tissue until the complete fin is regenerated.…”

Section: Introductionmentioning

confidence: 99%

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Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration

2013

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SUMMARYZebrafish have the capacity to regenerate several organs, including the heart and fins. Fin regeneration is epimorphic, involving the formation at the amputation plane of a mass of undifferentiated, proliferating mesenchymal progenitor-like cells, called blastema. This tissue provides all the cell types that form the fin, so that after damage or amputation the fin pattern and structure are fully restored. How blastema cells remain in this progenitor-like state is poorly understood. Here, we show that the Notch pathway plays an essential role during fin regeneration. Notch signalling is activated during blastema formation and remains active throughout the regeneration process. Chemical inhibition or morpholino-mediated knockdown of Notch signalling impairs fin regeneration via decreased proliferation accompanied by reduced expression of Notch target genes in the blastema. Conversely, overexpression of a constitutively active form of the Notch1 receptor (N1ICD) in the regenerating fin leads to increased proliferation and to the expansion of the blastema cell markers msxe and msxb, as well as increased expression of the proliferation regulator aldh1a2. This blastema expansion prevents regenerative fin outgrowth, as indicated by the reduction in differentiating osteoblasts and the inhibition of bone regeneration. We conclude that Notch signalling maintains blastema cells in a plastic, undifferentiated and proliferative state, an essential requirement for fin regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration

2013

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“…This suggests that Msx-1 can fully substitute for Bmp function during tail regeneration . Furthermore, induction of the same transgene after limb amputation is able to enhance limb regeneration at a stage when regeneration success is declining, although it is not able to rescue limb regeneration at nonregenerative stages (Barker and Beck, 2009). …”

Section: Bmp Signallingmentioning

confidence: 99%

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Beck

Belmonte

Christen

2009

Developmental Dynamics

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150

139

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While Xenopus is a well-known model system for early vertebrate development, in recent years, it has also emerged as a leading model for regeneration research. As an anuran amphibian, Xenopus laevis can regenerate the larval tail and limb by means of the formation of a proliferating blastema, the lens of the eye by transdifferentiation of nearby tissues, and also exhibits a partial regeneration of the postmetamorphic froglet forelimb. With the availability of inducible transgenic techniques for Xenopus, recent experiments are beginning to address the functional role of genes in the process of regeneration. The use of soluble inhibitors has also been very successful in this model. Using the more traditional advantages of Xenopus, others are providing important lineage data on the origin of the cells that make up the tissues of the regenerate. Finally, transcriptome analyses of regenerating tissues seek to identify the genes and cellular processes that enable successful regeneration.

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“…Culture of Xenopus laevis tadpoles has been described previously (Barker and Beck, 2009). Animals were staged according to Nieuwkoop and Faber, 1967.…”

Section: Amputation and Heat Shockmentioning

confidence: 99%

Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb

McEwan

Lynch

Beck

2011

Developmental Dynamics

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We have previously shown differential regulation of components of the Retinoic acid (RA) pathway in Xenopus tadpole hindlimb regeneration. RA is thought to act as a morphogen, providing positional information during development and regeneration. We have investigated the regulation of genes involved in RA synthesis, catabolism, and binding in developing and regenerating Xenopus limbs. Our data indicate that RA is synthesised by Raldh2 in proximal cells during limb bud outgrowth. Furthermore, Cyp26b is expressed transiently in the progress zone of developing limbs and the blastema of regenerating limbs suggesting degradation of RA occurs in both processes. The RA‐binding protein Crabp2 is also upregulated during regeneration. We summarise this data to predict the presence of evolving gradients of RA in the developing amphibian limb. Thus, RA from the stump cells could be responsible for the establishment of proximal‐distal pattern during limb regeneration, as predicted by classical studies. Developmental Dynamics 240:1259–1270, 2011. © 2011 Wiley‐Liss, Inc.

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Overexpression of the transcription factor Msx1 is insufficient to drive complete regeneration of refractory stage Xenopus laevis hindlimbs

Cited by 22 publications

References 55 publications

Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration

Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb

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