Regeneration in an evolutionarily primitive brain – the planarian Dugesia japonica model

Abstract

A unique aspect of planarians is that they can regenerate a brain from somatic pluripotent stem cells called neoblasts, which have the ability to produce themselves (self-renew) and to give rise to all missing cell types during regeneration. Recent molecular studies have revealed that the planarian brain is composed of many distinct neuronal populations, which are evolutionarily and functionally conserved ones, and acts as an information-processing center to elicit distinct behavioral traits depending on a variety of signals arising from the external environment. How can planarians regenerate such a brain? On the basis of our recent findings, here we review the cellular and molecular mechanisms that regulate the stem cell dynamics involved in the brain regeneration of the planarian Dugesia japonica. Our findings suggest the possible value of in vivo planarian studies for guiding regenerative medicine to treat neurodegenerative diseases via interlinking stem cell biology and regeneration biology.

Thermosensory Signaling by TRPM Is Processed by Brain Serotonergic Neurons to Produce Planarian Thermotaxis

“…Increasing knowledge has been gained recently about the morphogenesis of the planarian brain and its robust regenerative ability Reddien and Sanchez Alvarado, 2004;Shibata et al, 2010;Umesono et al, 2011;Umesono et al, 2013). Moreover, tractable planarian behavioral assay systems that can be quantified for many variables, such as time spent in a target zone, speed, and distance, and that can be used in combination with RNAi of neuron-specific genes, have provided molecular and cellular knowledge about the informationprocessing machinery in the brain Takano et al, 2007;.…”

“…Furthermore, planarians belong to an evolutionarily early group that acquired a CNS and show stereotypical behaviors in response to environmental stimuli (Pearl, 1903) perceived through sensory neurons projecting to an inverted U-shaped brain (Agata et al, 1998;Okamoto et al, 2005). Despite its relatively simple structure, the planarian brain is divided into several functional and structural domains composed of several types of neurons distinguished by their neurotransmitters and neural modulators, such as glutamate, dopamine, serotonin, GABA, acetylcholine, and neuropeptides, which are quite similar to those used by mammals (Umesono and Agata, 2009;Collins et al, 2010;Umesono et al, 2011).…”

An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

“…Adult stem cell populations (neoblasts) underlie their remarkable regenerative abilities (Reddien and Sánchez Alvarado, 2004;Wagner et al, 2011), and whole worms can regenerate from only a small proportion of the adult worm: a cut off (or damaged) head is rebuilt perfectly within few days (Inoue et al, 2004;Umesono et al, 2011). Recently, planarians have become a popular molecular-genetic system for the investigation of the pathways that allow complex structures such as the head to be regenerated after damage (Aboobaker, 2011;Gentile et al, 2011;Lobo et al, 2012;Newmark and Sánchez Alvarado, 2002;Saló et al, 2009;Sánchez Alvarado, 2006).…”

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

“…Activation of c-Jun-Nterminal kinase (JNK) after amputation induces G2/M transition and supplies blastema cells. Subsequently, activation of extracellular signal-related kinase (ERK) signalling is required for blastema cells to exit the undifferentiated state and enter the differentiation state in order to form the brain rudiment [27]. Similarly, activation of ERK signalling facilitates exit from selfrenewal and regulates differentiation signals, as in mouse ESCs [28].…”