A molecular wound response program associated with regeneration initiation in planarians

Abstract

Planarians are capable of regenerating any missing body part and present an attractive system for molecular investigation of regeneration initiation. The gene activation program that occurs at planarian wounds to coordinate regenerative responses remains unknown. We identified a large set of wound-induced genes during regeneration initiation in planarians. Two waves of wound-induced gene expression occurred in differentiated tissues. The first wave includes conserved immediate early genes. Many second-wave genes encode conserved patterning factors required for proper regeneration. Genes of both classes were generally induced by wounding, indicating that a common initial gene expression program is triggered regardless of missing tissue identity. Planarian regeneration uses a population of regenerative cells (neoblasts), including pluripotent stem cells. A class of wound-induced genes was activated directly within neoblasts, including the Runx transcription factor-encoding runt-1 gene. runt-1 was required for specifying different cell types during regeneration, promoting heterogeneity in neoblasts near wounds. Wound-induced gene expression in neoblasts, including that of runt-1, required SRF (serum response factor) and sos-1. Taken together, these data connect wound sensation to the activation of specific cell type regeneration programs in neoblasts. Most planarian wound-induced genes are conserved across metazoans, and identified genes and mechanisms should be important broadly for understanding wound signaling and regeneration initiation.

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

“…During bi-polar regeneration, β-catenin-1 is expressed in both blastemas (Iglesias et al, 2008). The secreted elements wnt1 and notum are first expressed in all wounds, and later become restricted to the posterior and anterior blastemas, respectively Reddien, 2009b, 2011;Wenemoser et al, 2012). Our results demonstrate that there is abundant nuclear β-CATENIN-1 in both anterior and posterior blastemas at any stage ( Fig.…”

Identification of neoblast- and regeneration-specific miRNAs in the planarian Schmidtea mediterranea

“…3A). Recent studies have shown that wound healing is initiated within 30 min of injury or amputation, which is followed by the migration of neoblasts to the site of injury (Wenemoser and Reddien 2010;Wenemoser et al 2012). Thus, the miRNAs that are up-regulated at 3 h and 6 h following amputation are the best candidates for investigating the role of miRNAs in wound healing and neoblast migration.…”

“…Recently, Wenemoser et al (2012) identified four categories of wound-induced gene expression patterns, which differ in their timing and location of expression. They also identified waves of gene expression, where the first wave (W1) of expression is initiated within 30 min of injury and tapers down within 24 h post-injury.…”

“…This complex phenomenon is controlled by a variety of genes that code for proteins involved in chromatin modifications, various signaling pathways, and post-transcriptional regulatory processes (Aboobaker et al 2011;Reddien et al 2011;King and Newmark 2012). Recently Wenemoser et al (2012) have identified waves of gene expression profiles that peak within 30 min following amputation and gradually taper down by 24 h, indicating tight regulation of gene expression during regeneration.…”

The NuRD complex componentp66suppresses photoreceptor neuron regeneration in planarians

“…2005b; Wenemoser et al. 2012). Prolonged inhibition of p66 in the absence of injury increased numbers of PRN progenitors ( ovo + otxA + cells) without affecting PCC progenitor numbers ( ovo + otxA − cells) (Fig.…”