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Cell Cycle Regulation and Regeneration

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New Perspectives in Regeneration

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 367))

Abstract

Regeneration of ear punch holes in the MRL mouse and amputated limbs of the axolotl show a number of similarities. A large proportion of the fibroblasts of the uninjured MRL mouse ear are arrested in G2 of the cell cycle, and enter nerve-dependent mitosis after injury to form a ring-shaped blastema that regenerates the ear tissue. Multiple cell types contribute to the establishment of the regeneration blastema of the urodele limb by dedifferentiation, and there is substantial reason to believe that the cells of this early blastema are also arrested in G2, and enter mitosis under the influence of nerve-dependent factors supplied by the apical epidermal cap. Molecular analysis reveals other parallels, such as; (1) the upregulation of Evi5, a centrosomal protein that prevents mitosis by stabilizing Emi1, a protein that inhibits the degradation of cyclins by the anaphase promoting complex and (2) the expression of sodium channels by the epidermis. A central feature in the entry into the cell cycle by MRL ear fibroblasts is a natural downregulation of p21, and knockout of p21 in wild-type mice confers regenerative capacity on non-regenerating ear tissue. Whether the same is true for entry into the cell cycle in regenerating urodele limbs is presently unknown.

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Abbreviations

AEC:

Apical epidermal cap

AGP:

Anterior gradient protein

APC:

Anaphase promoting complex

CDK:

Cyclin-dependent kinase

EGF:

Epidermal growth factor

FGF:

Fibroblast growth factor

G:

Gap

GGF:

Glial growth factor

HGF:

Hepatocyte growth factor

IGF:

Insulin-like growth factor

M:

Mitosis

PDGF:

Platelet-derived growth factor

RP:

Restriction point

S:

DNA synthesis

TGF:

Transforming growth factor

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Authors and Affiliations

  1. Wistar Institute, 3601 Spruce St., Philadelphia, PA, 19104, USA

    Ellen Heber-Katz, Yong Zhang & Khamila Bedelbaeva

  2. Department of Oral Biology, Indiana University School of Dentistry, Indiana University-Purdue University, Indianapolis, IN, 46202, USA

    Fengyu Song

  3. Department of Biology, School of Science, Indiana University-Purdue University, 723 W. Michigan St., Indianapolis, IN, 46202, USA

    Xiaoping Chen & David L. Stocum

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  1. Ellen Heber-Katz
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  2. Yong Zhang
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  3. Khamila Bedelbaeva
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  4. Fengyu Song
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  5. Xiaoping Chen
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  6. David L. Stocum
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Correspondence to Ellen Heber-Katz .

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Editors and Affiliations

  1. Wistar Institute, Spruce Street 3601, Philadelphia, 19104, Pennsylvania, USA

    Ellen Heber-Katz

  2. Center for Regenerative Biology and, Medicine, Indiana University, North Blackford Street 402, Indianapolis, 46202, Indiana, USA

    David L. Stocum

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Heber-Katz, E., Zhang, Y., Bedelbaeva, K., Song, F., Chen, X., Stocum, D.L. (2012). Cell Cycle Regulation and Regeneration. In: Heber-Katz, E., Stocum, D. (eds) New Perspectives in Regeneration. Current Topics in Microbiology and Immunology, vol 367. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_294

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