start-ver=1.4 cd-journal=joma no-vol=452 cd-vols= no-issue= article-no= start-page=104 end-page=113 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190815 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fgf- and Bmp-signaling regulate gill regeneration in Ambystoma mexicanum en-subtitle= kn-subtitle= en-abstract= kn-abstract= Gill regeneration has not been well studied compared to regeneration of other appendages, such as limb and tail regeneration. Here, we focused on axolotl gill regeneration and found that Fgf- and Bmp-signaling are involved in their gill regeneration mechanism. Axolotls have three pairs of gill rami, and each gill ramus has multiple gill filaments. The gills consist of mesenchyme rich in extracellular matrix and epidermis. The gill nerves are supplied from the trigeminal ganglia located in the head. Denervation resulted in no gill regeneration responses. Nerves and gills express Bmp and Fgf genes, and treating animals with Fgf- and Bmp-signaling inhibitors results in phenotypes similar to those seen in denervated gills. Inducing an accessory appendage is a standard assay in amphibian regeneration research. In our study, an accessory gill could be induced by lateral wounding, suggesting that thin axon fibers and mesenchymal Fgfs and Bmps contributed to the induction of the accessory structure. Such accessory gill induction was inhibited by the denervation. Exogenous Fgf2+Fgf8+Bmp7, which have been determined to function as a regeneration inducer in urodele amphibians, could compensate for the effects denervation has on accessory blastema formation. Our findings suggest that regeneration of appendages in axolotls is regulated by common Fgf- and Bmp-signaling cascades. en-copyright= kn-copyright= en-aut-name=Saito Nanami en-aut-sei=Saito en-aut-mei= Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Nishimura Koki en-aut-sei=Nishimura en-aut-mei= Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Makanae Aki en-aut-sei=Makanae en-aut-mei= Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=2 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=3 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=4 en-affil=Okayama University, Research Core for Interdisciplinary Sciences (RCIS) kn-affil= en-keyword=Blastema induction kn-keyword=Blastema induction en-keyword= Bmp kn-keyword= Bmp en-keyword=Fgf kn-keyword=Fgf en-keyword=Gill regeneration kn-keyword=Gill regeneration en-keyword=Nerve kn-keyword=Nerve en-keyword=Organ regeneration kn-keyword=Organ regeneration END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=9323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neural regulation in tooth regeneration of Ambystoma mexicanum en-subtitle= kn-subtitle= en-abstract= kn-abstract=The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. en-copyright= kn-copyright= en-aut-name=MakanaeAki en-aut-sei=Makanae en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TajikaYuki en-aut-sei=Tajika en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraKoki en-aut-sei=Nishimura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoNanami en-aut-sei=Saito en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaJun-Ichi en-aut-sei=Tanaka en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=2 en-affil=Gunma University, Department of Anatomy, Graduate School of Medicine kn-affil= affil-num=3 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=4 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=5 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= affil-num=6 en-affil=Okayama University Research Core for Interdisciplinary Sciences (RCIS) kn-affil= en-keyword=Cell proliferation kn-keyword=Cell proliferation en-keyword=Differentiation kn-keyword=Differentiation en-keyword=Morphogenesis kn-keyword=Morphogenesis END