4.4 Article

Apoptosis is required during early stages of tail regeneration in Xenopus laevis

Journal

DEVELOPMENTAL BIOLOGY
Volume 301, Issue 1, Pages 62-69

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2006.10.048

Keywords

Xenopus; tail; regeneration; apoptosis; otolith; neuron

Funding

  1. NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [K22DE016633] Funding Source: NIH RePORTER
  2. NCI NIH HHS [CO6RR11244] Funding Source: Medline
  3. NIDCR NIH HHS [1 K22 DE016633-01, K22 DE016633, K22 DE016633-02] Funding Source: Medline

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The Xenopus tadpole is able to regenerate its tail, including skin, muscle, notochord, spinal cord and neurons and blood vessels. This process requires rapid tissue growth and morphogenesis. Here we show that a focus of apoptotic cells appears in the regeneration bud within 12 h of amputation. Surprisingly, when caspase-3 activity is specifically inhibited, regeneration is abolished. This is true of tails both before and after the refractory period. Programmed cell death is only required during the first 24 h after amputation, as later inhibition has no effect on regeneration. Inhibition of caspase-dependent apoptosis results in a failure to induce proliferation in the growth zone, a mispatterning of axons in the regenerate, and the appearance of ectopic otoliths in the neural tube, in the context of otherwise normal continued development of the larva. Larvae amputated during the refractory stage exhibit a much broader domain of caspase-3-positive cells, suggesting a window for the amount of apoptosis that is compatible with normal regeneration. These data reveal novel roles for apoptosis in development and indicate that a degree of apoptosis is an early and obligate component of normal tail regeneration, suggesting the possibility of the existence of endogenous inhibitory cells that must be destroyed by programmed cell death for regeneration to occur. (c) 2006 Elsevier Inc. All rights reserved.

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