Coronel-Cordoba, P. | bioRxiv Science

bioRxiv2026

cWnt signaling regulates the early proliferative response and the differentiation of the neural, muscle and parenchymal tissues during planarian whole-body regeneration

Organizers, or signaling centers, play a central role in coordinating tissue growth, patterning, and differentiation during development and regeneration. In particular, organizers that arise during the regeneration of specific animal structures typically involve components of the canonical Wnt (cWnt) pathway and contribute to tissue growth and differentiation. However, how organizers and the cWnt pathway promote these processes in animals capable of whole-body regeneration remains poorly explored. Here, we analyze organizer functions in planarians, which can regenerate any missing body part from a population of adult pluripotent stem cells. The tips of the planarian body have been proposed to act as organizers. Here we demonstrate the organizing capacity of these tips by showing that anterior or posterior tips grafted into a host animal induce the formation of a patterned head or tail, respectively. Given that the cWnt inhibitor Notum and the activator Wnt1 define these tip regions, we next investigate the role of cWnt signaling in promoting growth and cell differentiation. Our results reveal that cWnt inhibition anteriorly and activation posteriorly are required to promote stem cell proliferation during regeneration. Furthermore, we show that repression and activation of cWnt signaling through {beta}catenin-1 and apc silencing, respectively, can rescue regeneration in sublethally irradiated planarians. Moreover, we show how cWnt signaling at posterior wounds is necessary for the differentiation of specific cell types, including neurons, muscle, and parenchymal cells. Together, our findings identify cWnt signaling as a key regulator of growth and cell differentiation within planarian organizing regions and provide new insight into how organizers control whole-body regeneration.

developmental biology↗

bioRxiv2020

Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians

Embryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. during regeneration, which also requires patterning of new tissues, remains unstudied. To that aim, we study regeneration in planarians, flatworms that can regenerate any missing structure, even the head, in a few days. In planarians, as described in embryonic models, the cWNT pathway specifies the anterior-posterior axis. During the first 12-24h after amputation both wnt1 and notum (a Wnt inhibitor) are expressed in any wound, but 48 hours later they become restricted to posterior or anterior facing wounds, forming the anterior and the posterior organizers, respectively. In this study we undertook a genomic approach to further understand the mechanism that triggers the early expression of wnt1 and the specification of the posterior identity. Through ATAC-sequencing and CHIPmentation techniques we uncovered Cis-Regulatory Elements of Schmidtea mediterranea genome and analyzed them in notum and wnt1 (RNAi) animals. The result shows that already at 12 hours after amputation the chromatin structure of the wounds has changed its conformation according to the polarity of the pre-existing tissue. Analysing the DNA binding motives present in the proximal regulatory regions of genes down-regulated after wnt1 (RNAi) we found a few genes containing a TCF binding site, which include posterior Homeobox genes and chromatin remodelling proteins, suggesting that those are direct targets of the cWNT pathway and the responsible to trigger the expression of the posterior effectors. Furthermore, we have identified FoxG as an up-stream regulator of wnt1 transcription, probably though binding to an enhancer found in its first intron. Silencing of foxG inhibits the early phase of wnt1 expression and phenocopies the wnt1 (RNAi) phenotype, indicating its early role in specifying posterior versus anterior identity. Moreover, we have created a new open platform to interpret all transcriptomic and genomic results obtained (https://compgen.bio.ub.edu/PlanNET/planexp).

developmental biology↗