Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro. We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema.
The authors declare no competing or financial interests.
Conceived and designed the experiments: N.A.B., C.P.P.; Performed the experiments: N.A.B.; Analyzed the data: N.A.B., C.P.P.; Contributed reagents/materials/analysis tools: N.A.B., C.P.P.; Wrote the paper: N.A.B., C.P.P.
This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) post-graduate scholarship (PGSD3-471547-2015 to N.A.B.); an Ellison Medical Foundation New Scholar in Aging Research Award (AG-NS-0835-11 to C.P.P.); and a National Institutes of Health Director's New Innovator Award (1DP2DE024365-01 to C.P.P.). Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.139964.supplemental
- Received May 17, 2016.
- Accepted December 30, 2016.