Apical epithelial cap morphology and fibronectin gene expression in regenerating axolotl limbs

Christensen, Randolph N.; Tassava, Roy A.

doi:10.1002/(sici)1097-0177(200002)217:2<216::aid-dvdy8>3.0.co;2-8

Cited by 97 publications

(85 citation statements)

References 60 publications

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“…Guidance by nerves was ruled out, since similar experiments on aneurogenic limbs also resulted in eccentric blastema formation (Thornton & Steen, 1962). Directional migration is provided by transforming growth factor β1 (TGF‐β1) stimulated fibronectin produced by basal cells of the AEC (Christensen & Tassava, 2000). Inhibition of TGF‐β1 expression by the inhibitor of SMAD phosphorylation, SB‐431542, reduces fibronectin expression, resulting in failure of blastema formation (Levesque et al., 2007).…”

Section: Formation Of the Accumulation Blastemamentioning

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: Formation Of the Accumulation Blastemamentioning

confidence: 99%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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“…TGF-b1 is strongly upregulated during blastema formation in amputated axolotl limbs (Levesque et al, 2007). A target gene of TGF-b1 is fibronectin, a substrate molecule for cell migration that is highly expressed by basal cells of the wound epidermis during blastema formation (Christensen and Tassava, 2000;Rao et al, 2009). Inhibition of TGF-b1 expression by the inhibitor of SMAD phosphorylation SB-431542 reduces fibronectin expression and results in failure of blastema formation (Levesque et al, 2007), suggesting that fibronectin produced by the AEC provides directional guidance for blastema cells.…”

Section: Mechanisms Of Blastema Cell Accumulationmentioning

confidence: 99%

Looking proximally and distally: 100 years of limb regeneration and beyond

Stocum

Cameron

2011

Developmental Dynamics

108

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The experimental study of amphibian limb regeneration spans most of the 20 th century and the first decade of the 21 st century. We first review the major questions investigated over this time span: (1) the origin of regeneration blastema cells, the mechanism of tissue breakdown that liberates cells from their tissue organization to participate in blastema formation, (3) the mechanism of dedifferentiation of these cells, (4) how the blastema grows, (5) how the blastema is patterned to restore the missing limb structures, and (6) why adult anurans, birds and mammals do not have the regenerative powers of urodele salamanders. We then look forward in a perspective to discuss the many unanswered questions raised by investigations of the past century, what new approaches can be taken to answer them, and what the prospects are for translation of basic research on limb regeneration into clinical means to regenerate human appendages. Developmental Dynamics 240:943-968,

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“…The layered morphology of the AEC, which develops from the wound epithelium at its apex, has been previously described in urodeles (Christensen and Tassava, 2000). In Xenopus hindlimbs that have been partially amputated before the ability to regenerate declines, a similar multilayered AEC is formed (Pearl et al, 2008).…”

Section: Histological Analyses Of M1 and Wt Tadpoles Reveal An Early mentioning

confidence: 82%

“…In both cases, the basal layer of epithelial cells, which directly contact the underlying mesenchyme, appeared cuboidal in shape, rather than columnar. Transition to columnar basal cell morphology is strongly associated with a functionally active AEC (Christensen and Tassava, 2000). Additionally, accumulation of eosin-stained connective tissue was almost always evident within the M1 blastema (six of seven cases examined, Fig.…”

Section: Histological Analyses Of M1 and Wt Tadpoles Reveal An Early mentioning

confidence: 85%

“…Concurrent with blastema formation and development is the transition of the simple wound epithelium into the multilayered apical epithelial cap (AEC). This transition occurs within the first 2 to 3 days during Xenopus hindlimb regeneration (Pearl et al, 2008) and is important in ensuring the blastema reaches a critical mass capable of driving complete limb regeneration in amphibians (Christensen and Tassava, 2000).…”

Section: Introductionmentioning

confidence: 99%

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

Barker

Beck

2009

Developmental Dynamics

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Xenopus laevis tadpoles are capable of hindlimb regeneration, although this ability declines with age. Bmp signaling is one pathway known to be necessary for successful regeneration to occur. Using an inducible transgenic line containing an activated version of the Bmp target Msx1, we assessed the ability of this transcription factor to enhance regeneration in older limbs. Despite considerable evidence correlating msx1 expression with regenerative success in vertebrate regeneration models, we show that induction of msx1 during hindlimb regeneration fails to induce complete regeneration. However, we did observe some improvement in regenerative outcome, linked to morphological changes in the early wound epithelium and a corresponding increase in proliferation in the underlying distal mesenchyme, neither of which are maintained later. Additionally, we show that Msx1 is not able to rescue limb regeneration in a Bmp signalling-deficient background, indicating that additional Bmp targets are required for regeneration in anuran limbs. Developmental Dynamics 238:1366 -1378, 2009.

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Apical epithelial cap morphology and fibronectin gene expression in regenerating axolotl limbs

Cited by 97 publications

References 60 publications

Mechanisms of urodele limb regeneration

Mechanisms of urodele limb regeneration

Looking proximally and distally: 100 years of limb regeneration and beyond

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

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