Reconstruction of dopaminergic neural network and locomotion function in planarian regenerates

Abstract

Planarian, an invertebrate flatworm, has a high capacity for regeneration when compared with other worms and animals. We show here for the first time that the reconstructed dopamine (DA) neural network regulates locomotion and behavior in planarian regenerates. The gene encoding tyrosine hydroxylase in the planarian Dugesia japonica (DjTH) was identified. DjTH protein was coexpressed with aromatic amino acid decarboxylase-like A (DjAADCA) in the planarian central nervous system (CNS). In addition, DjTH-knockdown planarians lost the ability to synthesize DA, but showed no change in 5-hydroxytryptamine synthesis. When the planarian body was amputated, DjTH-positive neurons were regenerated in the brain newly rebuilt from the tail piece at Day 3, and the DjTH-positive axonal and dendritic neural network in the CNS (dopaminergic tiara) was reconstructed at Days 5-7. At that time, autonomic locomotion and methamphetamine-induced hyperkinesia were also suppressed in DjTH-knockdown planarians. Planarian locomotion and behavior seem to be regulated in both cilia-and muscle-dependent manners. In DjTH-knockdown planarians, muscle-mediated locomotion and behavior were significantly attenuated. These results suggest that DA neurons play a key role in the muscle-mediated movement in planarians.

Brain regeneration from pluripotent stem cells in planarian

“…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). Also, additional functional domains in the planarian brain have been defined by gene expression analyses, and give us a more complex view of this organ than suggested by its relatively simple morphology (Cebrià et al 2002a).…”

Planarian Hedgehog/Patched establishes anterior–posterior polarity by regulating Wnt signaling

“…anti-DjAADCA antibody (15) revealed that Djptc(RNAi) regenerants showed posterior fate in the anterior region, as indicated by their bifurcated branching (Fig. 1L).…”

“…38. After whole-mount in situ hybridization, specimens were subjected to immunohistochemistry using anti-DjAADCA or anti-DjSyt antibody essentially as described (15,32). In brief, specimens were incubated with the primary antibody (1:1,000 dilution) overnight at 4°C.…”

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

“…We recently discovered that the planarian CNS contains dopamine, serotonin, γ-aminobutyric acid (GABA) and acetylcholine, which are known to be present in mammalians, and that the planarian nervous system constitutes particular neural networks and functions [15][16][17][18][19]. Since planarians possess pluripotent stem cells throughout their entire bodies, their CNS can be completely regenerated along with recovery of morphology and function after amputation [20].…”

“…One involves DA neuroregeneration accompanied by brain regeneration after artificial amputation [15,21]. The other involves DA neuronal regeneration after selective degeneration of DA neurons by the DA neurotoxin 6-hydroxydopamine (6-OHDA) [22].…”