Reactive Oxygen Species in Planarian Regeneration: An Upstream Necessity for Correct Patterning and Brain Formation.

Nicky Pirotte,Marcel Ameloot,Susanna Fraguas,Michelle Plusquin,Rik Paesen,Andromeda Van Roten,An-Sofie Stevens,Tom Artois,Francesc Cebrià,Karen Smeets,Frank Van Belleghem

doi:10.1155/2015/392476

Abstract

Recent research highlighted the impact of ROS as upstream regulators of tissue regeneration. We investigated their role and targeted processes during the regeneration of different body structures using the planarian Schmidtea mediterranea, an organism capable of regenerating its entire body, including its brain. The amputation of head and tail compartments induces a ROS burst at the wound site independently of the orientation. Inhibition of ROS production by diphenyleneiodonium (DPI) or apocynin (APO) causes regeneration defaults at both the anterior and posterior wound sites, resulting in reduced regeneration sites (blastemas) and improper tissue homeostasis. ROS signaling is necessary for early differentiation and inhibition of the ROS burst results in defects on the regeneration of the nervous system and on the patterning process. Stem cell proliferation was not affected, as indicated by histone H3-P immunostaining, fluorescence-activated cell sorting (FACS), in situ hybridization of smedwi-1, and transcript levels of proliferation-related genes. We showed for the first time that ROS modulate both anterior and posterior regeneration in a context where regeneration is not limited to certain body structures. Our results indicate that ROS are key players in neuroregeneration through interference with the differentiation and patterning processes.

Highlights

Reactive oxygen species (ROS) exert a dual role in cells, tissues, and organs [1,2,3]
Our results supplement previous findings as we investigated the effects of an impaired ROS burst on processes such as proliferation, differentiation, and patterning
The orientation of the wound did not influence the intensity of the amputation-induced ROS burst, but the ROS burst at both wound sites of the trunk fragments was less intense compared to the ROS-induced fluorescence at the wound sites of the head and tail fragments (Figure 1; supplementary Figure 1(A))

Summary

Introduction

Reactive oxygen species (ROS) exert a dual role in cells, tissues, and organs [1,2,3]. The cellular redox signaling modulates various physiological processes including immunology, development, neurological functioning, wound healing, and angiogenesis [1, 2, 4, 5]. Many studies show that regenerative animals are less vulnerable to aging and are less likely to develop tumors [8, 12,13,14]. As such, these animal models are crucial to fully understand the regeneration process to overcome or reverse unwanted diseases. Accumulating evidence suggests that controlling the intraand extracellular redox balance holds the answer for the treatment of multiple conditions. de Barros and colleagues (2013) showed that manipulation of ROS signaling (using hypoxic preconditioning) increases the angiogenic capacities of human adipose stroma/stem cells, thereby improving their application in medical therapies [16]

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Conclusion