Gene Expression during Amphibian Limb Regeneration

Géraudie, Jacqueline; Ferretti, Patrizia

doi:10.1016/s0074-7696(08)61769-6

Cited by 76 publications

(48 citation statements)

References 204 publications

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“…The cell growth and maintenance proteins include specific keratins that were identified in previous immunocytochemical studies as up-regulated in adult newt limb regeneration (see Discussion). Many other abundant proteins listed in Table 2, including matrix metalloproteinases, fibronectin, type I collagen, vimentin, and non-muscle myosin have also been found to be expressed or concentrated more highly in regenerating adult urodele limbs using unrelated methods (reviewed by Geraudie and Ferretti, 1998). Our identification here of many specific proteins shown by other investigators to appear after limb amputation in other species and using completely different experimental techniques, strongly supports the validity of the proteomics approach to the understanding of the regulation of regeneration in this system.…”

Section: Statistically Significant Proteins In Regenerating Blastemasmentioning

confidence: 99%

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

2009

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During amphibian epimorphic limb regeneration, local injury produces metabolic changes that lead to cellular dedifferentiation and formation of a blastema, but few details of these changes have been elucidated. Here we report the first global proteomic analysis of epimorphic regeneration comparing the profiles of abundant proteins in larval limbs of the anuran Xenopus laevis (stage 53) at the time of amputation (0dPA) and 3 days post-amputation when the regeneration blastema is developing (3dPA). We identified and quantified 1517 peptides, of which 1067 were identified with high peptide ID confidence. Of these 1067 proteins, 489 showed significant changes in quantity between the two groups. Taking into account identical peptides whose fold changes were within 20%, and not including peptides whose fold changes were below the observed fold changes of peptides for the internal standard (chicken lysozyme), we were able to identify 145 peptides elevated in 3dPA relative to 0dPA and 220 peptides in 0dPA relative to 3dPA. In this report, we focus on those proteins that were elevated in the 3dPA tissue relative to 0dPA. In this class were members of the annexin family (e.g. ANXA1, ANXA2, ANXA5) and the ANXA2-binding partner S100A10, which have important immunoregulatory roles in other systems and were also shown to be differentially expressed in stage 53 and 57 3dPA and 5dPA blastemas in our previous microarray studies. Besides elucidating the possible modulation of inflammation during amphibian limb regeneration, our proteomic study also provides insight into dedifferentiation by revealing up-regulation of proteins known to characterize many stem cells.

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Section: Statistically Significant Proteins In Regenerating Blastemasmentioning

confidence: 99%

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

2009

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“…Among adult tetrapods such regeneration is restricted to urodele amphibians, but regeneration involving similar mechanisms also occurs in fins of many teleost fishes and in the developing limbs of larval anuran amphibians. Limbs of adult anurans, like those of other vertebrates, fail to regenerate after amputation or do so without normal patterning (Geraudie and Ferretti, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Expression of many genes or other molecular markers in specific cells of regenerating amphibian limbs has been found empirically (Geraudie and Ferretti, 1998). More recently, differential screening approaches for genes expressed in regenerating Xenopus limbs or tails have provided additional insights into molecular events important for regeneration (Ishino et al, 2003;King et al, 2003;Tazaki et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Global analysis of gene expression inXenopushindlimbs during stage‐dependent complete and incomplete regeneration

Grow

Neff

Mescher

et al. 2006

Developmental Dynamics

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Xenopus laevis tadpoles are capable of limb regeneration after amputation, in a process that initially involves the formation of a blastema. However, Xenopus has full regenerative capacity only through premetamorphic stages. We have used the Affymetrix Xenopus laevis Genome Genechip microarray to perform a large-scale screen of gene expression in the regeneration-complete, stage 53 (st53), and regeneration-incomplete, stage 57 (st57), hindlimbs at 1 and 5 days postamputation. Through an exhaustive reannotation of the Genechip and a variety of comparative bioinformatic analyses, we have identified genes that are differentially expressed between the regeneration-complete and -incomplete stages, detected the transcriptional changes associated with the regenerating blastema, and compared these results with those of other regeneration researchers. We focus particular attention on striking transcriptional activity observed in genes associated with patterning, stress response, and inflammation. Overall, this work provides the most comprehensive views yet of a regenerating limb and different transcriptional compositions of regeneration-competent and deficient tissues.

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“…The lepidotrichia are composed of two segmented hemirays that bifurcate periodically along their proximal-distal axis forming sister-ray branches. After amputation, epithelial cells migrate from the stump to cover the wound region (7,8), beneath which a blastema containing undifferentiated proliferative mesenchymal cells forms (1). Scleroblasts then differentiate within the blastema at the epithelial͞mesenchymal interface and begin to secrete the matrix that will form the new dermal bone.…”

mentioning

confidence: 99%

Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine

Quint

Smith

Avaron

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

187

207

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Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in the secretion and patterning of the regenerating dermal bone, but a direct role has not been demonstrated. We established an in vivo method of gene transfection to express ectopically genes in the blastema of regenerating fins. Ectopic expression of shh or bmp2 in the blastema-induced excess bone deposition and altered patterning of the regenerate. The effects of shh ectopic expression could be antagonized by ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp) signaling. We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme. Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression. These results implicate shh and bmp2b signaling in the proliferation and͞or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin.T he extent of regenerative capacity varies between species and tissue types. Analysis of the regenerative events is not only informative in its own right but may also provide information pertaining to earlier morphogenetic events, because regeneration often recapitulates development. An example of this is the dermal skeleton component of the zebrafish (Danio rerio) caudal fin, which regenerates rapidly after amputation by processes reminiscent of those occurring during larval stages (for review, see ref. 1), including reexpression of developmental genes (2-6).The dermal skeleton of the zebrafish fin comprises mineralized lepidotrichia (fin rays) and more distal collagenous actinotrichia (Fig. 1A). The lepidotrichia are composed of two segmented hemirays that bifurcate periodically along their proximal-distal axis forming sister-ray branches. After amputation, epithelial cells migrate from the stump to cover the wound region (7, 8), beneath which a blastema containing undifferentiated proliferative mesenchymal cells forms (1). Scleroblasts then differentiate within the blastema at the epithelial͞mesenchymal interface and begin to secrete the matrix that will form the new dermal bone.During regeneration, the signaling molecule sonic hedgehog (shh) involved in patterning of many structures (reviewed in ref. 9), its membrane-receptor patched1 (ptc1) (9), and bone morphogenetic protein 2b (bmp2b), a member of the transforming growth factor-␤ family (10), are all initially reexpressed in a single domain at the distal stump of the amputated ray. Expression is found in a subset of cells in the basal layer of the epider...

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Gene Expression during Amphibian Limb Regeneration

Cited by 76 publications

References 204 publications

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

Global analysis of gene expression inXenopushindlimbs during stage‐dependent complete and incomplete regeneration

Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine

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