Dissecting planarian central nervous system regeneration by the expression of neural‐specific genes

Abstract

The planarian central nervous system (CNS) can be used as a model for studying neural regeneration in higher organisms. Despite its simple structure, recent studies have shown that the planarian CNS can be divided into several molecular and functional domains defined by the expression of different neural genes. Remarkably, a whole animal, including the molecularly complex CNS, can regenerate from a small piece of the planarian body. In this study, a collection of neural markers has been used to characterize at the molecular level how the planarian CNS is rebuilt. Planarian CNS is composed of an anterior brain and a pair of ventral nerve cords that are distinct and overlapping structures in the head region. During regeneration, 12 neural markers have been classified as early, mid-regeneration and late expression genes depending on when they are upregulated in the regenerative blastema. Interestingly, the results from this study show that the comparison of the expression patterns of different neural genes supports the view that at day one of regeneration, the new brain appears within the blastema, whereas the pre-existing ventral nerve cords remain in the old tissues. Three stages in planarian CNS regeneration are suggested.

Reconsidering regeneration in metazoans: an evo-devo approach

“…Also, transient structures like the blastema are not always useful for comparative studies across distant taxa. Where blastemas can be characterized by a mass of cells clustering in the area of the wound after closure, leading to growth and regeneration into new organs or new body parts, it has been shown that the histological nature of this mass of cells is different in different regenerative structures (Shibata et al, 1999;Cebrià et al, 2002;Bosch et al, 2008;Kragl et al, 2009;Wenemoser and Reddien, 2010;Aboobaker, 2011;Reddien, 2013;Bely et al, 2014). Additionally in some epimorphic regenerative events, i.e., where local stimulation of cell proliferation precedes the development of the new part, there is a lack of structures that resemble a blastema, such as during the Ciona intestinalis siphon regeneration (Auger et al, 2010) or the whole body regeneration in colonial ascidians (Brown et al, 2009b).…”

Brain regeneration from pluripotent stem cells in planarian

“…We investigated precisely how the neurons in each domain are connected by analysing the projection patterns of each domain in detail by DiI/DiD tracing (Okamoto et al 2005). Also, we found that a planarian netrin homologue (Djnetrin) is expressed in the junctions between visual neurons and the brain as well as between the VNCs and the brain (Cebrià et al 2002c;Cebrià & Newmark 2005). These analyses suggested that a variety of external signals received by these sensory neurons may be integrated in the DjotxBexpressing domain, where dopaminergic neurons are concentrated (Nishimura et al 2007), and that these integrated signals may be transferred to the body muscles through the VNCs (Tazaki et al 1999).…”

“…Interestingly, most of these genes are expressed in distinct domains of the intact brain and at distinct stages during the brain regeneration. They can be classified into four classes according to their expression timing during the process of brain regeneration: early; early-middle; late-middle; and late genes (Cebrià et al 2002c ). These results suggested that clathrin-mediated endocytic signals may be required not only for the maintenance of neurons after synaptic formation, but also for axonal extension at the early stage of brain regeneration.…”

A Survey of the Molecular Basis for the Generation of Functional Dopaminergic Neurons from Pluripotent Stem Cells: Insights from Regenerative Biology and Regenerative Medicine

“…Large-scale expression analyses have revealed that many neural genes involved in vertebrate brain development and function are also expressed in distinct domains of the planarian CNS [13,14]. These results indicate that the planarian CNS is functionally regionalized according to a discrete expression of neural-specific genes.…”