Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.

TitleIon channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.
Publication TypeJournal Article
Year of Publication2017
JournalMechanisms of development
Volume146
Pagination42-54
ISSN0925-4773
Abstract

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K2.1, K2.2, L-type Cachannels and H/K ATPases) or completely (GlyR, GABAR, K1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in tail muscle and mesenchymal regions. Inhibition of anoctamin 1/2 also altered the post-amputation transcriptional response of p44/42 MAPK signaling pathway genes, including decreased expression of erk1/erk2. We also found that complete inhibition via voltage gated Kchannel blockade was associated with diminished phagocyte recruitment to the amputation site. The identification of Hpumps as required for axolotl tail regeneration supports findings in Xenopus and Planaria models, and more generally, the conservation of ion channels as regulators of tissue regeneration. This study provides a preliminary framework for an in-depth investigation of the mechanistic role of ion channels and their potential involvement in regulating cellular proliferation and other processes essential to wound healing, appendage regeneration, and tissue repair.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0925-4773(17)30083-7
DOI10.1016/j.mod.2017.06.001
Short TitleMech Dev
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