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Dev Cell January 1, 2018; 46 (4): 397-409.e5.

Melanocortin Receptor 4 Signaling Regulates Vertebrate Limb Regeneration.

Zhang M , Chen Y , Xu H , Yang L , Yuan F , Li L , Xu Y , Chen Y , Zhang C , Lin G .

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.

PubMed ID: 30130530
PMC ID: PMC6107305
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: agrp atp5f1a atp5f1c cox5a cox7b crem cyb5a cyba cyc1 fgf10 fos grem1 hhip hoxa13 hoxc10 ihh mapk1 mc1r mc2r mc3r mc4r mc5r mmd msx1 ndufs1 ndufs2 ndufs3 ndufs7 pcna pdgfra pitx1 pomc prrx1 ror2 sall4 sdha sdhb tbx4 tubb3 uqcrfs1
GO keywords: animal organ regeneration
Morpholinos: mc4r MO1 mc4r MO2

Article Images: [+] show captions
References [+] :
Anderson, 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH. 2017, Pubmed