Midkine is a dual regulator of wound epidermis development and inflammation during the initiation of limb regeneration

Abstract

Formation of a specialized wound epidermis is required to initiate salamander limb regeneration. Yet little is known about the roles of the early wound epidermis during the initiation of regeneration and the mechanisms governing its development into the apical epithelial cap (AEC), a signaling structure necessary for outgrowth and patterning of the regenerate. Here, we elucidate the functions of the early wound epidermis, and further reveal midkine (mk) as a dual regulator of both AEC development and inflammation during the initiation of axolotl limb regeneration. Through loss- and gain-of-function experiments, we demonstrate that mk acts as both a critical survival signal to control the expansion and function of the early wound epidermis and an anti-inflammatory cytokine to resolve early injury-induced inflammation. Altogether, these findings unveil one of the first identified regulators of AEC development and provide fundamental insights into early wound epidermis function, development, and the initiation of limb regeneration.

Divergent Influenza-Like Viruses of Amphibians and Fish Support an Ancient Evolutionary Association

“…The presence of this viral genome in up to four species of Ambystoma colonies indicates that it potentially has a wide host range across this host genus. Additionally, as the majority of A. mexicanum colonies originate from the Ambystoma Genetic Stock Center (AGSC, University of Kentucky, KY, USA) [ 45 , 46 , 47 , 48 ] and in some cases co-housed together with other species positive for this virus [ 43 ], this virus may circulate between numerous laboratory-reared salamander colonies.…”

“…The presence of this viral genome in up to four species of Ambystoma colonies indicates that it potentially has a wide host range across this host genus. Additionally, as the majority of A. mexicanum colonies originate from the Ambystoma Genetic Stock Center (AGSC, University of Kentucky, KY, USA) [45][46][47][48] and in some cases co-housed together with other species positive for this virus [43], this virus may circulate between numerous laboratory-reared salamander colonies. Supplementary Tables S1-S6 and Figures S1-S5. We similarly identified an influenza virus in the Siamese algae-eater (Gyrinocheilus aymonieri) (SRA accession: SRR5997773), tentatively termed Siamese algae-eater influenza-like virus, sampled as part of the Fish-T1K Project (Table 1) [28].…”

A constitutively expressed fluorescence ubiquitin cell cycle indicator (FUCCI) in axolotls for studying tissue regeneration

“…The formation of the blastema is dependent on an intact nerve supply and a specialized layer of epithelium known as the apical epithelial cap (AEC) (McCusker et al, 2015a). The AEC likely has multiple functions including directing outgrowth, maintaining proliferation, and secreting factors that allow for remodeling of underlying extracellular matrix (Stocum, 2017; Tsai et al, 2020). Although the blastema consists of numerous cell types, most cells originate from mesenchymal cell populations located near the amputation plane (Butler, 1933; McHedlishvili et al, 2007).…”

Heterogeneouspdgfrβ+cells regulate coronary vessel development and revascularization during heart regeneration

“…S6A, B, C). Midkine (mdk) has been shown to play important roles in tissue regeneration in many different organs (Ang et al, 2020, Ikutomo et al, 2014, Tsai et al, 2020. However, in contrast to pdgfrb mutant hearts, mdka mutants did not show significant defects in heart regeneration (Fig.…”