4.3 Article

Apoptosis is a generator of Wnt-dependent regeneration and homeostatic cell renewal in the ascidian Ciona

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BIOLOGY OPEN
卷 10, 期 4, 页码 -

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COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.058526

关键词

Regeneration; Homeostasis; Ciona; Apoptosis; Wnt signaling; Stem cells

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资金

  1. National Institutes of Health [AG055411]
  2. European Marine Biological Resource Centre, France

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In the ascidian Ciona intestinalis, regeneration and homeostatic growth involve the activity of adult stem cells in the branchial sac, with apoptosis and Wnt signaling playing key roles. Apoptosis has different effects in regeneration and homeostatic growth processes.
In the ascidian Ciona intestinalis, basal body parts regenerate distal structures but distal body parts do not replace basal structures. Regeneration involves the activity of adult stem cells in the branchial sac, which proliferate and produce migratory progenitor cells for tissue and organ replacement. Branchial sac-derived stem cells also replenish recycling cells lining the pharyngeal fissures during homeostatic growth. Apoptosis at injury sites occurs early during regeneration and continuously in the pharyngeal fissures during homeostatic growth. Caspase 1 inhibitor, caspase 3 inhibitor, or pan-caspase inhibitor Z-VAD-FMK treatment blocked apoptosis, prevented regeneration, and suppressed branchial sac growth and function. A pharmacological screen and siRNA-mediated gene knockdown indicated that regeneration requires canonical Wnt signaling. Wnt3a protein rescued both caspase-blocked regeneration and branchial sac growth. Inhibition of apoptosis did not affect branchial sac stem cell proliferation but prevented the survival of progenitor cells. After bisection across the mid-body, apoptosis occurred only in the regenerating basal fragments, although both fragments contained a part of the branchial sac, suggesting that apoptosis is unilateral at the wound site and the presence of branchial sac stem cells is insufficient for regeneration. The results suggest that apoptosis-dependent Wnt signaling mediates regeneration and homeostatic growth in Ciona.

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