Refining the Ciona intestinalis Model of Central Nervous System Regeneration

Abstract

BackgroundNew, practical models of central nervous system regeneration are required and should provide molecular tools and resources. We focus here on the tunicate Ciona intestinalis, which has the capacity to regenerate nerves and a complete adult central nervous system, a capacity unusual in the chordate phylum. We investigated the timing and sequence of events during nervous system regeneration in this organism.Methodology/Principal FindingsWe developed techniques for reproducible ablations and for imaging live cellular events in tissue explants. Based on live observations of more than 100 regenerating animals, we subdivided the regeneration process into four stages. Regeneration was functional, as shown by the sequential recovery of reflexes that established new criteria for defining regeneration rates. We used transgenic animals and labeled nucleotide analogs to describe in detail the early cellular events at the tip of the regenerating nerves and the first appearance of the new adult ganglion anlage.Conclusions/SignificanceThe rate of regeneration was found to be negatively correlated with adult size. New neural structures were derived from the anterior and posterior nerve endings. A blastemal structure was implicated in the formation of new neural cells. This work demonstrates that Ciona intestinalis is as a useful system for studies on regeneration of the brain, brain-associated organs and nerves.

The nervous system of the adult ascidian Ciona intestinalis Type A (Ciona robusta): Insights from transgenic animal models

“…In the previous studies, the visceral nerve was identified as an unpaired nerve in Ciona [13,52–54]. In contrast, we identified “paired” visceral nerves.…”

Evolution of the chordate regeneration blastema: Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona

“…Since Notch signaling was previously shown to be involved in central and peripheral nervous system development in ascidian embryos and larvae (Akanuma et al, 2002; Pasini et al, 2006; Hudson et al, 2007; Chen et al, 2011), the possible function of the Notch pathway during adult neural regeneration would be an important subject for future study. Furthermore, during the Ciona life span, the capacity for regeneration continuously declines until it is compromised near the end of life (Dahlberg et al, 2009; Auger et al, 2010; Jeffery, 2012). As a part of this decreased regeneration capacity, there is a reduction in the potency of stem cells located in the branchial sac (Jeffery, 2015b), possibly as a consequence of aging effects on the Notch signaling system.…”

“…Regeneration is probably more limited in solitary ascidians, such as Ciona intestinalis , in which distal body parts can be replaced from proximal parts, as long as the latter contain a portion of the branchial sac (Hirschler, 1914; Jeffery, 2015a). In Ciona , the oral siphon (OS), a muscular tube leading into the mucus-forming pharynx, and the neural complex, which includes the brain and the associated neural gland, are able to regenerate with complete fidelity within about a month after their removal (Sutton, 1953; Whittaker, 1975; Bollner, et al, 1992; 1993; 1995; Dahlberg et al, 2009; Auger et al, 2010). The OS pigment organs (OPO), which are sensory receptors rimming the siphon opening (Dilly and Wolken, 1973), and the circular muscle fibers lying immediately below them, reappear more rapidly, within about 5–10 days after amputation (Auger et al, 2010).…”

Ciona intestinalis and Oxycomanthus japonicus, Representatives of Marine Invertebrates

“…Usually Ciona researchers use embryos; they collect eggs and sperm from the supplied animals, and the gametes are used for each experiment. Ciona adults have also been used as materials to study physiology, regeneration and biochemistry [7,22]. In 2009, the Misaki Marine Biological Station of the University of Tokyo, began supporting part of this project.…”