Jeffery William R.

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William R.

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  • Preprint
    Closing the wounds : one hundred and twenty five years of regenerative biology in the ascidian Ciona intestinalis
    ( 2014-06) Jeffery, William R.
    This year marks the 125th anniversary of the beginning of regeneration research in the ascidian Ciona intestinalis. A brief note was published in 1891 reporting the regeneration of the Ciona neural complex and siphons. This launched an active period of Ciona regeneration research culminating in the demonstration of partial body regeneration: the ability of proximal body parts to regenerate distal ones, but not vice versa. In a process resembling regeneration, wounds in the siphon tube were discovered to result in the formation of an ectopic siphon. Ciona regeneration research then lapsed into a period of relative inactivity following the purported demonstration of the inheritance of acquired characters using siphon regeneration as a model. Around the turn of the present century, Ciona regeneration research experienced a new blossoming. The current studies established the morphological and physiological integrity of the regeneration process and its resemblance to ontogeny. They also determined some of the cell types responsible for tissue and organ replacement and their sources in the body. Finally, they showed that regenerative capacity is reduced with age. Many other aspects of regeneration now can be studied at the mechanistic level because of the extensive molecular tools available in Ciona.
  • Preprint
    Evolution of the chordate regeneration blastema : differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona
    ( 2015-06) Hamada, Mayuko ; Goricki, Spela ; Byerly, Mardi S. ; Satoh, Noriyuki ; Jeffery, William R.
    The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration.
  • Preprint
    Regeneration of oral siphon pigment organs in the ascidian Ciona intestinalis
    ( 2009-12-06) Auger, Helene ; Sasakura, Yasunori ; Joly, Jean-Stephane ; Jeffery, William R.
    Ascidians have powerful capacities for regeneration but the underlying mechanisms are poorly understood. Here we examine oral siphon regeneration in the solitary ascidian Ciona intestinalis. Following amputation, the oral siphon rapidly reforms oral pigment organs (OPO) at its distal margin prior to slower regeneration of proximal siphon parts. The early stages of oral siphon reformation include cell proliferation and re-growth of the siphon nerves, although the neural complex (adult brain and associated organs) is not required for regeneration. Young animals reform OPO more rapidly after amputation than old animals indicating that regeneration is age dependent. UV irradiation, microcautery, and cultured siphon explant experiments indicate that OPOs are replaced as independent units based on local differentiation of progenitor cells within the siphon, rather than by cell migration from a distant source in the body. The typical pattern of eight OPOs and siphon lobes is restored with fidelity after distal amputation of the oral siphon, but as many as sixteen OPOs and lobes can be reformed following proximal amputation near the siphon base. Thus, the pattern of OPO regeneration is determined by cues positioned along the proximal distal axis of the oral siphon. A model is presented in which columns of siphon tissue along the proximal-distal axis below pre-existing OPO are responsible for reproducing the normal OPO pattern during regeneration. This study reveals previously unknown principles of oral siphon and OPO regeneration that will be important for developing Ciona as a regeneration model in urochordates, which may be the closest living relatives of vertebrates.
  • Article
    Distal regeneration involves the age dependent activity of branchial sac stem cells in the ascidian Ciona intestinalis
    (John Wiley & Sons, 2014-11-13) Jeffery, William R.
    Tunicates have high capacities for regeneration but the underlying mechanisms and their relationship to life cycle progression are not well understood. Here we investigate the regeneration of distal structures in the ascidian tunicate Ciona intestinalis. Analysis of regenerative potential along the proximal−distal body axis indicated that distal organs, such as the siphons, their pigmented sensory organs, and the neural complex, could only be replaced from body fragments containing the branchial sac. Distal regeneration involves the formation of a blastema composed of cells that undergo cell proliferation prior to differentiation and cells that differentiate without cell proliferation. Both cell types originate in the branchial sac and appear in the blastema at different times after distal injury. Whereas the branchial sac stem cells are present in young animals, they are depleted in old animals that have lost their regeneration capacity. Thus Ciona adults contain a population of age-related stem cells located in the branchial sac that are a source of precursors for distal body regeneration.
  • Preprint
    Regeneration, stem cells, and aging in the tunicate Ciona : insights from the oral siphon
    ( 2015-04) Jeffery, William R.
    Regeneration studies in the tunicate Ciona intestinalis have recently been focused on the potential of adult stem cells to replace injured tissues and organs during the adult life cycle using the oral siphon (OS) as a model. The OS has oral siphon pigment organs (OPO) along its rim and an underlying network of muscle fibers in its tube. Different regeneration processes are triggered by OS amputation at the tip, along the tube, or at the base. One process involves the replacement of OPO without new cell division by direct differentiation of locally deployed stem cells or stem cells that migrate from the branchial sac. Another process involves blastema formation by the migration of progenitor cells produced from branchial sac stem cells. The capacity for complete and accurate OS regeneration declines continuously during the adult life cycle. Finally, after an age threshold is reached, OS regeneration ceases in old animals. The loss of regeneration capacity in old animals involves the depletion of stem cells in the branchial sac, the inability of brachial sac progenitor cells to migrate to the sites of regeneration, and defective OPO replacement. The significance of the OS model for studying regeneration, stem cells, and aging will be enhanced by the application of molecular methods.
  • Article
    The tunicate Ciona : a model system for understanding the relationship between regeneration and aging
    (Taylor & Francis, 2014-06-10) Jeffery, William R.
    The use of the tunicate Ciona intestinalis as a model system to study the relationship between regeneration and aging is reviewed. Ciona has powerful regeneration capacities, which fade with age. Some additional benefits are a relatively short life span, the ability to study regeneration in vitro, the close phylogenetic relationship between tunicates and vertebrates, and the host of molecular tools already established in this system. The neural complex (NC), the oral siphon (OS), and the oral siphon pigment organs (OPO) have high capacities for regeneration. However, these organs show an inverse relationship between rate of regeneration and age. The ability to regenerate a complete OS disappears in the oldest animals of a natural population, probably due to the inability to form a blastema at the wound site. Effects on blastema formation could also be involved in the reduction of NC regeneration capacity. The fidelity of OPO restoration is also compromised by excess differentiation of precursor cells in local siphon niches in the oldest animals. The Ciona model provides a pathway to understand the molecular basis of these phenomena.