Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration

Regeneration of a complex appendage structure such as limb requires upstream and downstream coordination of multiple types of cells. Given type of cell may sit at higher upstream position to control the activities of other cells. Muscles are one of the major cell masses in limbs. However, the subtle...

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Main Authors: Yan Hu, Xiangyu Pan, Yu Shi, Yuanhui Qiu, Liqun Wang, Prayag Murawala, Yanmei Liu, Wanjin Xing, Elly M. Tanaka, Ji-Feng Fei
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.1036641/full
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author Yan Hu
Xiangyu Pan
Xiangyu Pan
Yu Shi
Yuanhui Qiu
Liqun Wang
Prayag Murawala
Prayag Murawala
Yanmei Liu
Wanjin Xing
Elly M. Tanaka
Ji-Feng Fei
author_facet Yan Hu
Xiangyu Pan
Xiangyu Pan
Yu Shi
Yuanhui Qiu
Liqun Wang
Prayag Murawala
Prayag Murawala
Yanmei Liu
Wanjin Xing
Elly M. Tanaka
Ji-Feng Fei
author_sort Yan Hu
collection DOAJ
description Regeneration of a complex appendage structure such as limb requires upstream and downstream coordination of multiple types of cells. Given type of cell may sit at higher upstream position to control the activities of other cells. Muscles are one of the major cell masses in limbs. However, the subtle functional relationship between muscle and other cells in vertebrate complex tissue regeneration are still not well established. Here, we use Pax7 mutant axolotls, in which the limb muscle is developmentally lost, to investigate limb regeneration in the absence of skeletal muscle. We find that the pattern of regenerated limbs is relative normal in Pax7 mutants compared to the controls, but the joint is malformed in the Pax7 mutants. Lack of muscles do not affect the early regeneration responses, specifically the recruitment of macrophages to the wound, as well as the proliferation of fibroblasts, another major population in limbs. Furthermore, using single cell RNA-sequencing, we show that, other than muscle lineage that is mostly missing in Pax7 mutants, the composition and the status of other cell types in completely regenerated limbs of Pax7 mutants are similar to that in the controls. Our study reveals skeletal muscle is barely required for the guidance of other cells, as well the patterning in complex tissue regeneration in axolotls, and provides refined views of the roles of muscle cell in vertebrate appendage regeneration.
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spelling doaj.art-83c938b9369a47219405c295511cc9002022-12-22T03:30:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-10-011310.3389/fgene.2022.10366411036641Muscles are barely required for the patterning and cell dynamics in axolotl limb regenerationYan Hu0Xiangyu Pan1Xiangyu Pan2Yu Shi3Yuanhui Qiu4Liqun Wang5Prayag Murawala6Prayag Murawala7Yanmei Liu8Wanjin Xing9Elly M. Tanaka10Ji-Feng Fei11Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaDepartment of Medical Research, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaMDI Biological Laboratory, Bar Harbor, ME, United StatesClinic for Kidney and Hypertension Diseases, Hannover Medical School, Hannover, GermanyKey Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaInner Mongolia Key Laboratory for Molecular Regulation of the Cell, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaRegeneration of a complex appendage structure such as limb requires upstream and downstream coordination of multiple types of cells. Given type of cell may sit at higher upstream position to control the activities of other cells. Muscles are one of the major cell masses in limbs. However, the subtle functional relationship between muscle and other cells in vertebrate complex tissue regeneration are still not well established. Here, we use Pax7 mutant axolotls, in which the limb muscle is developmentally lost, to investigate limb regeneration in the absence of skeletal muscle. We find that the pattern of regenerated limbs is relative normal in Pax7 mutants compared to the controls, but the joint is malformed in the Pax7 mutants. Lack of muscles do not affect the early regeneration responses, specifically the recruitment of macrophages to the wound, as well as the proliferation of fibroblasts, another major population in limbs. Furthermore, using single cell RNA-sequencing, we show that, other than muscle lineage that is mostly missing in Pax7 mutants, the composition and the status of other cell types in completely regenerated limbs of Pax7 mutants are similar to that in the controls. Our study reveals skeletal muscle is barely required for the guidance of other cells, as well the patterning in complex tissue regeneration in axolotls, and provides refined views of the roles of muscle cell in vertebrate appendage regeneration.https://www.frontiersin.org/articles/10.3389/fgene.2022.1036641/fullaxolotllimb regenerationsalamandersingle cell RNA sequencingknockoutPax7
spellingShingle Yan Hu
Xiangyu Pan
Xiangyu Pan
Yu Shi
Yuanhui Qiu
Liqun Wang
Prayag Murawala
Prayag Murawala
Yanmei Liu
Wanjin Xing
Elly M. Tanaka
Ji-Feng Fei
Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
Frontiers in Genetics
axolotl
limb regeneration
salamander
single cell RNA sequencing
knockout
Pax7
title Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
title_full Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
title_fullStr Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
title_full_unstemmed Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
title_short Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
title_sort muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration
topic axolotl
limb regeneration
salamander
single cell RNA sequencing
knockout
Pax7
url https://www.frontiersin.org/articles/10.3389/fgene.2022.1036641/full
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