Melanocortin Receptor 4 Signaling Regulates Vertebrate Limb Regeneration

Mengshi Zhang, Youwei Chen, Hanqian Xu, Li Yang, Feng Yuan, Lei Li, Ying Xu, Ying Chen, Chao Zhang, Gufa Lin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Melanocortin 4 receptor (Mc4r) plays a crucial role in the central control of energy homeostasis, but its role in peripheral organs has not been fully explored. We have investigated the roles of hypothalamus-mediated energy metabolism during Xenopus limb regeneration. We report that hypothalamus injury inhibits Xenopus tadpole limb regeneration. By loss-of-function and gain-of-function studies, we show that Mc4r signaling is required for limb regeneration in regeneration-competent tadpoles and stimulates limb regeneration in later-stage regeneration-defective tadpoles. It regulates limb regeneration through modulating energy homeostasis and ROS production. Even more interestingly, our results demonstrate that Mc4r signaling is regulated by innervation and α-MSH substitutes for the effect of nerves in limb regeneration. Mc4r signaling is also required for mouse digit regeneration. Thus, our findings link vertebrate limb regeneration with Mc4r-mediated energy homeostasis and provide a new avenue for understanding Mc4r signaling in the peripheral organs. Zhang et al. describe a requirement for melanocortin receptor 4 (Mc4r) signaling in tadpole limb and mouse digit regeneration. They show that Mc4r signaling regulates energy homeostasis and ROS production in the regenerating limb. In addition, α-MSH/Mc4r signaling can substitute for the effect of innervation on limb regeneration.

Original languageEnglish (US)
Pages (from-to)397-409.e5
JournalDevelopmental Cell
Volume46
Issue number4
DOIs
StatePublished - Aug 20 2018

Bibliographical note

Funding Information:
The authors thank Dr. Jonathan Slack for critical reading of the manuscript. The authors are grateful to Dr. Huxing Cui for sharing the Mc4r-gfp transgenic mice with us. This work was supported by research grants from the National Natural Science Foundation of China (31571491, 31771608, 81570760, and 31771283), the Science and Technology Commission of Shanghai Municipality (15PJ1407200), the Ministry of Science and Technology of China (2017YFA0103900, 2017YFA0103902, 2016YFA0102200), and the National Institute of Child Health and Human Development NIH (R01HD084440).

Funding Information:
The authors thank Dr. Jonathan Slack for critical reading of the manuscript. The authors are grateful to Dr. Huxing Cui for sharing the Mc4r-gfp transgenic mice with us. This work was supported by research grants from the National Natural Science Foundation of China ( 31571491 , 31771608 , 81570760 , and 31771283 ), the Science and Technology Commission of Shanghai Municipality ( 15PJ1407200 ), the Ministry of Science and Technology of China ( 2017YFA0103900 , 2017YFA0103902 , 2016YFA0102200 ), and the National Institute of Child Health and Human Development NIH ( R01HD084440 ).

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Mc4r
  • POMC
  • ROS
  • Xenopus
  • digit regeneration
  • energy metabolism
  • limb regeneration
  • neurotrophic factor
  • α-MSH

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