Planarian regeneration: achievements and future directions after 20 years of research

Abstract

Planarians can undergo dramatic changes in body size and regenerate their entire body plan from small pieces after cutting. This remarkable morphological plasticity has made them an excellent model in which to analyze phenomena such as morphogenesis, restoration of pattern and polarity, control of tissue proportions and tissue homeostasis. They have a unique population of pluripotent stem cells in the adult that can give rise to all differentiated cell types, including the germ cells. These cellular characteristics provide an excellent opportunity to study the mechanisms involved in the maintenance and differentiation of cell populations in intact and regenerating animals. Until recently, the planarian model system lacked opportunities for genetic analysis; however, this handicap was overcome in the last decade through the development of new molecular methods which have been successfully applied to planarians. These techniques have allowed analysis of the temporal and spatial expression of genes, as well as interference with gene function, generating the first phenotypes by loss or gain of function. Finally, the sequencing of the planarian genome has provided the essential tools for an in-depth analysis of the genomic regulation of this model system. In this review, we provide an overview of planarians as a model system for research into development and regeneration and describe new lines of investigation in this area.

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

“…During the last decade, planarians have become an important model organism in the field of developmental and regenerative biology; because of their extensive regenerative capacity (driven by an adult stem cell population) and complex CNS, significant efforts are underway to understand the molecular mechanisms behind neural repair and patterning (Aoki et al, 2009;Gentile et al, 2011;Newmark and Sánchez Alvarado, 2002;Nishimura et al, 2011;Saló et al, 2009;Sánchez Alvarado, 2006;Tanaka and Reddien, 2011;Umesono and Agata, 2009). However, because of their rich behavioral repertoire and ability to learn (Corning, 1967;, this model system also has the potential to offer unique opportunities for understanding the dynamics of memory during brain regeneration.…”

“…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). Thus, planarians are an ideal system in which to probe the dynamics of information stored in the CNS during massive remodeling and repair.…”

The Hydra model: disclosing an apoptosis-driven generator of Wnt-based regeneration

“…Indeed, in adulthood, both models show: 1) a continuous tissue replacement due to a stock of mitotically active stem cells (unique in planarians -the neoblasts -, triple in Hydra -the ectodermal epithelial, endodermal epithelial and interstitial stem cells; 2) a stock of adult pluripotent stem cells that produce throughout the life of the animals both germ cells and somatic cells [12][13][14][15] (a rather special case in eumetazoans that usually segregate their germ cells during early embryonic development); 3) an efficient asexual reproduction (budding in Hydra, fission in planaria); 4) the amazing property to regenerate almost any missing part of the body after injury; 5) an apparent lack of aging, at least as long as the animals are kept asexual [16][17][18] . Molecular and cellular tools to dissect the mechanisms underlying regeneration have been developed recently in both model systems.…”

Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation

“…Planarians (phylum Platyhelminthes, class Turbellaria) are bilaterian, triploblastic free-living flatworms best known for their impressive ability to regenerate lost body parts (Morgan, 1898;Saló et al, 2009;Forsthoefel, 2009). This extreme plasticity is due to the presence of a large population (20-30% of the total number of cells) (Hay and Coward, 1975;Baguñà, 1976;Baguñà and Romero, 1981;Newmark and Sánchez Alvarado, 2000;Hayashi et al, 2006) of somatic pluripotent stem cells known as neoblasts (Dubois, 1949;Wolff, 1962).…”