Go ahead, grow a head! A planarian's guide to anterior regeneration

Abstract

The unique ability of some planarian species to regenerate a head de novo, including a functional brain, provides an experimentally accessible system in which to study the mechanisms underlying regeneration. Here, we summarize the current knowledge on the key steps of planarian head regeneration (head-versus-tail decision, anterior pole formation and head patterning) and their molecular and cellular basis. Moreover, instructive properties of the anterior pole as a putative organizer and in coordinating anterior midline formation are discussed. Finally, we highlight that regeneration initiation occurs in a two-step manner and hypothesize that wound-induced and existing positional cues interact to detect tissue loss and together determine the appropriate regenerative outcomes.

Keywords: Organizer; Wnt; patterning; planaria; polarity; regeneration; wound.

Figure 1

Two phases of wnt1/notum expression and function. In uninjured animals, notum is expressed at the anterior pole and anterior commissure in the brain, while wnt1 is expressed at the posterior pole. During regeneration, both genes are induced at all wounds in a dispersed ‘salt and pepper’ pattern in the early phase, although notum expression is higher in anterior‐facing blastemas. In the late phase, notum and wnt1 expression clusters at the anterior‐most and posterior‐most tips of the fragment, respectively, the regeneration poles. As regeneration continues, notum and wnt1 expression domains elongate until the homeostatic pattern is restored.

Figure 2

Juxtaposition of tissues with different positional identities induces intercalary regeneration. Differential expression of position control genes, biophysical properties and presence of different tissues manifest positional identities along the AP (1−8; 1 is most anterior, 8 is most posterior) and DV (A−D; A is dorsal, D is ventral) axes. (A) Grafting head fragments onto pharyngeal areas induces intercalary regeneration of the missing anterior areas (Reddien & Sanchez Alvarado 2004). (B) Reversing the orientation of a prepharyngeal graft along the DV axis induces generation of ectopic outgrowths (Kato et al. 1999). (C) Grafting posterior fragments into anterior areas induces development of outgrowths and regeneration of new pharynges on either side of the outgrowth (Kobayashi et al. 1999). In contrast, grafts from posterior tissues into tail areas or anterior tissues into prepharyngeal areas did not induce formation of outgrowths (Kobayashi et al. 1999).

Figure 3

Graded competences along the body axes and their interactions with wound‐induced patterning signals may determine the regenerative outcome. (A) Under homeostatic conditions, posteriorizing signals (e.g., Wnt1) are expressed in the tail (orange gradient), while their inhibitors (e.g., Notum) are more highly expressed in the anterior (blue gradient). This creates graded competences along the AP axis, resulting in anterior tissues that are more competent to produce and respond to anterior‐promoting signals and less competent to produce and respond to posterior‐promoting signals, and vice versa. (B) Anterior‐ and posterior‐promoting patterning genes are wound induced (blue and orange dots) and communicate with surrounding positional information in the existing tissues. Because of the graded competence of cells in this tissue, neighbor‐to‐neighbor interactions and interactions with wound‐induced signals may result in predominantly anterior‐promoting signals (blue arrows) at anterior‐facing blastemas and posterior‐promoting signals (orange arrows) at posterior‐facing blastemas of amputated animals. In contrast, anterior‐promoting and posterior‐promoting signals may be balanced at incisions that do not involve tissue loss, resolving the wound‐induced signals and resulting in no regeneration.