研究者詳細 - 佐藤　伸

論文 - 佐藤　伸

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Co-operative Bmp- and Fgf-signaling inputs convert skin wound healing to limb formation in urodele amphibians 査読

Aki Makanae, Kazumasa Mitogawa, Akira Satoh

DEVELOPMENTAL BIOLOGY 396 ( 1 ) 57 - 66 2014年12月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

Urodele amphibians have remarkable organ regeneration capability, and their limb regeneration capability has been investigated as a representative phenomenon. In the early 19th century, nerves were reported to be an essential tissue for the successful induction of limb regeneration. Nerve substances that function in the induction of limb regeneration responses have long been sought. A new experimental system called the accessory limb model CALM) has been established to identify the nerve factors. Skin wounding in urodele amphibians results in skin wound healing but never in limb induction. However, nerve deviation to the wounded skin induces limb formation in ALM. Thus, nerves can be considered to have the ability to transform skin wound healing to limb formation. In the present study, co-operative Bmp and Fgf application, instead of nerve deviation, to wounded skin transformed skin wound healing to limb formation in two urodele amphibians, axolotl (Ambystoma mexicanum) and newt (Pleurodeles waltl): Our findings demonstrate that defined factors can induce homeotic transformation in postembryonic bodies of urodele amphibians. The combination of Bmp and Fgf(s) may contribute to the development of novel treatments for organ regeneration. (C) 2014 The Authors. Published by Elsevier Inc.

DOI： 10.1016/j.ydbio.2014.09.021

Keratinocyte-driven dermal collagen formation in the axolotl skin 査読

Ayaka Ohashi, Hirotaka Sakamoto, Junpei Kuroda, Yohei Kondo, Yasuhiro Kamei, Shigenori Nonaka, Saya Furukawa, Sakiya Yamamoto, Akira Satoh

Nature Communications 16 ( 1 ) 2025年2月

Collagen fiber and cellular dynamics of axolotl skin with aging 査読

Shima C., Ohashi A., Furukawa S., Yamamoto S., Kashmoto R., Satoh A., co-first auhotrs

Development, Growth and Differentiation in press 2025年2月

Allometry in limb regeneration and scale-invariant patterning as the basis of normal morphogenesis from different sizes of blastemas 査読

Furukawa. S, Yamamoto S, Ohashi A, Morishita Y*, Satoh A*, Co-correspondence authors

Development 151 ( 21 ) 2024年

Tenascin-C-enriched regeneration-specific extracellular matrix guarantees superior muscle regeneration in Ambystoma mexicanum 査読

Developmental Biology in press 2023年10月

FGF signaling induces the regeneration of collagen fiber structure during skin wound healing in axolotls 査読

Rena Kashimoto, Yasuhiro Kamei, Shigenori Nonaka, Yohei Kondo, Sakiya Yamamoto, Saya Furukawa, Ayaka Ohashi, Akira Satoh

Developmental Biology 498 14 - 25 2023年3月

Bead Implantation and Delivery of Exogenous Growth Factors. 国際誌

Rena Kashimoto, Saya Furukawa, Sakiya Yamamoto, Akira Satoh

Methods in molecular biology (Clifton, N.J.) 2562 209 - 216 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

Genetic methods in axolotls (Ambystoma mexicanum) remain in their infancy which has hampered the study of limb regeneration. There is much room for advancement, especially with respect to spatiotemporal regulation of gene expression. Secreted growth factors play a major role in each stage of regeneration. The use of slow-release beads is one of the most effective methods to control the spatiotemporal expression of secretory gene products. The topical administration of secreted factors by slow-release beads may also prove effective for future applications in non-regenerative animals and for medical applications in humans, in which genetic methods are not available. In this chapter, we describe a methodology for using and implanting slow-release beads to deliver exogenous growth factors to salamanders.

DOI： 10.1007/978-1-0716-2659-7_14

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Lattice-patterned collagen fibers and their dynamics in axolotl skin regeneration 査読

Rena Kashimoto, Saya Furukawa, Sakiya Yamamoto, Yasuhiro Kamei, Joe Sakamoto, Shigenori Nonaka, Tomonobu M. Watanabe, Tatsuya Sakamoto, Hirotaka Sakamoto, Akira Satoh

iScience 25 ( 7 ) 104524 - 104524 2022年6月

An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration 招待査読国際誌

Satoh A, Kashimoto R, Ohashi A, Furukawa S, Yamamoto S, Inoue T, Hayashi T, Agata K

Zoological letters in press ( 1 ) 6 - 6 2022年5月

Lmx1b activation in axolotl limb regeneration 査読国際誌

Sakiya Yamamoto, Rena Kashimoto, Saya Furukawa, Ayaka Ohashi, Akira Satoh

Developmental Dynamics 2022年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

BACKGROUND: Axolotls can regenerate their limbs. In their limb regeneration process, developmental genes are re-expressed and reorganize the developmental axes, in which the position-specific genes are properly re-expressed. However, how such position specificity is reorganized in the regeneration processes has not been clarified. To address this issue, we focused on the reactivation process of Lmx1b, which determines the limb dorsal identity in many animals. RESULTS: Here, we show that Lmx1b expression is maintained in the dorsal skin before amputation and is activated after amputation. Furthermore, we demonstrate that only cells located in the dorsal side prior to limb amputation could reactivate Lmx1b after limb amputation. We also found that Lmx1b activation was achieved by nerve presence. The nerve factors, BMP2+FGF2+FGF8 (B2FF), consistently reactivate Lmx1b when applied to the dorsal skin. CONCLUSIONS: These results imply that the retained Lmx1b expression in the intact skin plays a role in positional memory, which instruct cells about the spatial positioning before amputation. This memory is reactivated by nerves or nerve factors that can trigger the entire limb regeneration process. Our findings highlight the role of nerves in amphibian limb regeneration, including both the initiation of limb regeneration and the reactivation of position-specific gene expression.

DOI： 10.1002/dvdy.476

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/dvdy.476

Graphene oxide-based multi-component antimicrobial hydrogels 招待査読

Zahedul Islam Nizami, M.Z.I, Campéon B.D.L, Satoh A, Nishina Y

Bulletin of the Chemical Society of Japan in press 2022年4月

Variable Shh and Fgf8 positioning in regenerating axolotl limb guarantees consistent limb morphogenesis in different limb sizes

Saya Furukawa, Sakiya Yamamoto, Rena Kashimoto, Yoshihiro Morishita, Akira Satoh

2022年1月

出版者・発行元：Cold Spring Harbor Laboratory

Abstract

Limb regeneration in Ambystoma mexicanum occurs in various size fields and can recreate consistent limb morphology. The mechanism that supports such stable limb morphogenesis regardless of size is unknown. Sonic hedgehog (SHH) and fibroblasts growth factor 8 (FGF8) play important roles in anteroposterior limb patterning, similar to other tetrapods. Focusing on these two factors, we investigated the detailed expression pattern and function of Shh and Fgf8 in various blastema sizes in axolotl limb regeneration. We measured and functionally analyzed the expression domains of Shh and Fgf8 in regenerating limb blastema of various sizes, and found that, although the position and size of the Shh⁺ and Fgf8⁺ domains varied depending on the size of the blastema, the secretion of SHH was maintained at a relatively fixed working distance, regardless of blastema size. This stable secretory distance of SHH resulted in the formation of an active proliferative zone (aPZ) in the vicinity of SHH, regardless of blastema size. The aPZ was under the mitogenic influence of SHH and FGF8, resulting in high cell density in the aPZ. We also examined the impact of the aPZ on digit formation. We found that the first digit formation occurs in the aPZ. Next, the aPZ gradually shifts posteriorly as digits develop, which contributes to new digit formation at the site of the shifted aPZ. We also found that the exogenously formed aPZ caused extra digit formation even after the completion of autopod morphogenesis. Our findings suggest that the variable Shh-Fgf8 positioning in various blastema sizes causes various positioning of the aPZ, and that the aPZ leads to digit formation. The mechanism we propose here accounts for stable digit morphogenesis regardless of blastema sizes and urodele-specific digit formation.

One-Sentence Summary

A unique SHH-FGF8 spatial interaction compensates for robust limb morphogenesis in various limb sizes.

DOI： 10.1101/2022.01.04.475010

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Nerve-mediated FGF-signaling in the early phase of various organ regeneration. 査読国際誌

Sakiya Yamamoto, Rena Kashimoto, Saya Furukawa, Hirotaka Sakamoto, Akira Satoh

Journal of experimental zoology. Part B, Molecular and developmental evolution 336 ( 7 ) 529 - 539 2021年8月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Amphibians have a very high capacity for regeneration among tetrapods. This superior regeneration capability in amphibians can be observed in limbs, the tail, teeth, external gills, the heart, and some internal organs. The mechanisms underlying the superior organ regeneration capability have been studied for a long time. Limb regeneration has been investigated as the representative phenomenon for organ-level regeneration. In limb regeneration, a prominent difference between regenerative and nonregenerative animals after limb amputation is blastema formation. A regeneration blastema requires the presence of nerves in the stump region. Thus, nerve regulation is responsible for blastema induction, and it has received much attention. Nerve regulation in regeneration has been investigated using the limb regeneration model and newly established alternative experimental model called the accessory limb model. Previous studies have identified some candidate genes that act as neural factors in limb regeneration, and these studies also clarified related events in early limb regeneration. Consistent with the nervous regulation and related events in limb regeneration, similar regeneration mechanisms in other organs have been discovered. This review especially focuses on the role of nerve-mediated fibroblast growth factor in the initiation phase of organ regeneration. Comparison of the initiation mechanisms for regeneration in various amphibian organs allows speculation about a fundamental regenerative process.

DOI： 10.1002/jez.b.23093

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Axolotl liver regeneration is accomplished via compensatory congestion mechanisms regulated by ERK signaling after partial hepatectomy. 査読国際誌

Ayaka Ohashi, Nanami Saito, Rena Kashimoto, Saya Furukawa, Sakiya Yamamoto, Akira Satoh

Developmental dynamics : an official publication of the American Association of Anatomists 2020年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Axolotls have remarkable organ-level regeneration capability. They can regenerate their limbs, tail, brain, gills, and heart. The liver had been considered to be a regenerative organ in these highly regeneration-competent animals. Therefore, no research had been performed on liver regeneration in urodele amphibians. In the present study, we focused on axolotl liver regeneration and found a unique regeneration mechanism compared with other vertebrates. RESULTS: Partial hepatectomy (PH) was performed to assess axolotl liver regeneration. Regeneration was assessed using block-face imaging (CoMBi), histology, cell proliferation, weight gain, and Albumin (Alb) + area. Axolotl liver histology was compared with other vertebrates. Axolotl liver consists of Glisson's capsule, sinusoids, and hepatic cord with no apparent lobule structures. Hepatocytes were mononucleated or multinucleated. PH increased the multinucleated hepatocytes and the Alb + area, but there was no apparent liver shape recovery even 40 days after PH. Gene expression pattern suggests that no epimorphic regeneration takes place. We also found that the increase in the number of proliferating hepatocytes was regulated by ERK-signaling. CONCLUSION: Our findings suggest that axolotls, which have epimorphic regeneration ability, regenerate their liver via unique mechanisms, compensatory congestion.

DOI： 10.1002/dvdy.262

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Neural regulation in tooth regeneration of Ambystoma mexicanum. 査読国際誌

Aki Makanae, Yuki Tajika, Koki Nishimura, Nanami Saito, Jun-Ichi Tanaka, Akira Satoh

Scientific reports 10 ( 1 ) 9323 - 9323 2020年6月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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.

DOI： 10.1038/s41598-020-66142-2

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Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum. 査読

Iwata R, Makanae A, Satoh A

Developmental dynamics : an official publication of the American Association of Anatomists 2019年8月

Fgf- and Bmp-signaling regulate gill regeneration in Ambystoma mexicanum. 査読

Saito N, Nishimura K, Makanae A, Satoh A

Developmental biology 452 ( 2 ) 104 - 113 2019年8月

Ectopic Fgf signaling induces the intercalary response in developing chicken limb buds 査読

Aki Makanae, Akira Satoh

Zoological Letters 4 ( 1 ) 8 2018年4月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BioMed Central Ltd.

Background: Intercalary pattern formation is an important regulatory step in amphibian limb regeneration. Amphibian limb regeneration is composed of multiple steps, including wounding, blastema formation, and intercalary pattern formation. Attempts have been made to transfer insights from regeneration-competent animals to regeneration-incompetent animalsat each step in the regeneration process. In the present study, we focused on the intercalary mechanism in chick limb buds. In amphibian limb regeneration, a proximodistal axis is organized as soon as a regenerating blastema is induced. Intermediate structures are subsequently induced (intercalated) between the established proximal and distal identities. Intercalary tissues are derived from proximal tissues. Fgf signaling mediates the intercalary response in amphibian limb regeneration. Results: We attempted to transfer insights into intercalary regeneration from amphibian models to the chick limb bud. The zeugopodial part was dissected out, and the distal and proximal parts were conjunct at st. 24. Delivering ectopic Fgf2 + Fgf8 between the distal and proximal parts resulted in induction of zeugopodial elements. Examination of HoxA11 expression, apoptosis, and cell proliferation provides insights to compare with those in the intercalary mechanism of amphibian limb regeneration. Furthermore, the cellular contribution was investigated in both the chicken intercalary response and that of axolotl limb regeneration. Conclusions: We developed new insights into cellular contribution in amphibian intercalary regeneration, and found consistency between axolotl and chicken intercalary responses. Our findings demonstrate that the same principal of limb regeneration functions between regeneration-competent and-incompetent animals. In this context, we propose the feasibility of the induction of the regeneration response in amniotes.

DOI： 10.1186/s40851-018-0090-2

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Hyperinnervation improves Xenopus laevis limb regeneration 査読

Kazumasa Mitogawa, Aki Makanae, Akira Satoh

Developmental Biology 433 ( 2 ) 276 - 286 2018年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier Inc.

Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches. These pattern defects are thought to be caused by loss of proper expressions of patterning-related genes. This study shows that hyperinnervation surgery resulted in the induction of a branching regenerate. The hyperinnervated blastema allows the identification and functional analysis of the molecules controlling this patterning of limb regeneration. This paper focuses on the nerve affects to improve Xenopus limb patterning ability during regeneration. The nerve molecules, which regulate limb patterning, were also investigated. Blastemas grown in a hyperinnervated forelimb upregulate limb patterning-related genes (shh, lmx1b, and hoxa13). Nerves projecting their axons to limbs express some growth factors (bmp7, fgf2, fgf8, and shh). Inputs of these factors to a blastema upregulated some limb patterning-related genes and resulted in changes in the cartilage patterns in the regenerates. These results indicate that additional nerve factors enhance Xenopus limb patterning-related gene expressions and limb regeneration ability, and that bmp, fgf, and shh are candidate nerve substitute factors.

DOI： 10.1016/j.ydbio.2017.10.007

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Nerve roles in blastema induction and pattern formation in limb regeneration. 査読

Satoh A, Mitogawa K, Makanae A

The International journal of developmental biology 62 ( 9-10 ) 605 - 612 2018年

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