activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis

Autoři: Jennifer K. Cloutier aff001;  Conor L. McMann aff001;  Isaac M. Oderberg aff001;  Peter W. Reddien aff001
Působiště autorů: Whitehead Institute for Biomedical Research, Cambridge, MA, United States of America aff001;  Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America aff002;  Howard Hughes Medical Institute, Chevy Chase, MD, United States of America aff003;  Harvard/MIT MD-PhD, Harvard Medical School, Boston, MA, United States of America aff004
Vyšlo v časopise: activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis. PLoS Genet 17(3): e1009466. doi:10.1371/journal.pgen.1009466
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009466


Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition of activin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, positional information is constitutively expressed in muscle to maintain proper patterning. Positional information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of positional information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonist notum at anterior-facing over posterior-facing wounds. Asymmetric activation of notum represents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown. activin-2 RNAi animals displayed symmetric wound-induced activation of notum at anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype. activin-2 RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration.

Klíčová slova:

Gene expression – Head regeneration – Muscle cells – Planarians – Regeneration – RNA interference – Wnt signaling cascade – Surgical amputation


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