Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells

BMC Biology

Research Article

Consuelo Anguita-Salinas¹  Miguel L. Allende¹  Daniela Gutiérrez¹  Mario Sánchez¹  Maria Laura Ceci¹ 

[1] FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Las Palmeras 3425, Santiago, Chile;

关键词: Zebrafish;    Regeneration;    Neuromast;    ErbB;    Schwann cell;    Lateral line;   

DOI  :  10.1186/s12915-016-0249-2

 received in 2015-12-08, accepted in 2016-03-22,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundRegenerating damaged tissue is a complex process, requiring progenitor cells that must be stimulated to undergo proliferation, differentiation and, often, migratory behaviors and morphological changes. Multiple cell types, both resident within the damaged tissue and recruited to the lesion site, have been shown to participate. However, the cellular and molecular mechanisms involved in the activation of progenitor cell proliferation and differentiation after injury, and their regulation by different cells types, are not fully understood. The zebrafish lateral line is a suitable system to study regeneration because most of its components are fully restored after damage. The posterior lateral line (PLL) is a mechanosensory system that develops embryonically and is initially composed of seven to eight neuromasts distributed along the trunk and tail, connected by a continuous stripe of interneuromastic cells (INCs). The INCs remain in a quiescent state owing to the presence of underlying Schwann cells. They become activated during development to form intercalary neuromasts. However, no studies have described if INCs can participate in a regenerative event, for example, after the total loss of a neuromast.ResultsWe used electroablation in transgenic larvae expressing fluorescent proteins in PLL components to completely ablate single neuromasts in larvae and adult fish. This injury results in discontinuity of the INCs, Schwann cells, and the PLL nerve. In vivo imaging showed that the INCs fill the gap left after the injury and can regenerate a new neuromast in the injury zone. Further, a single INC is able to divide and form all cell types in a regenerated neuromast and, during this process, it transiently expresses the sox2 gene, a neural progenitor cell marker. We demonstrate a critical role for Schwann cells as negative regulators of INC proliferation and neuromast regeneration, and that this inhibitory property is completely dependent on active ErbB signaling.ConclusionsThe potential to regenerate a neuromast after damage requires that progenitor cells (INCs) be temporarily released from an inhibitory signal produced by nearby Schwann cells. This simple yet highly effective two-component niche offers the animal robust mechanisms for organ growth and regeneration, which can be sustained throughout life.

【 授权许可】

CC BY   
© Sánchez et al. 2016