XB-ART-56792Evol Dev July 1, 2020; 22 (4): 297-311.
von Willebrand factor D and EGF domains is an evolutionarily conserved and required feature of blastemas capable of multitissue appendage regeneration.
Regenerative ability varies tremendously across species. A common feature of regeneration of appendages such as limbs, fins, antlers, and tails is the formation of a blastema-a transient structure that houses a pool of progenitor cells that can regenerate the missing tissue. We have identified the expression of von Willebrand factor D and EGF domains (vwde) as a common feature of blastemas capable of regenerating limbs and fins in a variety of highly regenerative species, including axolotl (Ambystoma mexicanum), lungfish (Lepidosiren paradoxa), and Polpyterus (Polypterus senegalus). Further, vwde expression is tightly linked to the ability to regenerate appendages in Xenopus laevis. Functional experiments demonstrate a requirement for vwde in regeneration and indicate that Vwde is a potent growth factor in the blastema. These data identify a key role for vwde in regenerating blastemas and underscore the power of an evolutionarily informed approach for identifying conserved genetic components of regeneration.
PubMed ID: 32163674
PMC ID: PMC7390686
Article link: Evol Dev
Genes referenced: egf
GO keywords: regeneration
Article Images: [+] show captions
|Figure 1. von willebrand factor D and EGF‐like domains (vwde) is a blastema‐enriched gene that is found across deuterostomes. (a) vwde (contig c1084387_g3_i1) expression in FPKM across tissues sampled from Bryant et al. (2017). Proximal and distal blastema samples are combined. (b–e) RNA in situ hybridization for vwde at (b) wound healing (3 days postamputation), (c) early‐bud blastema, (d) medium‐bud blastema, and (e) palette stage regenerating limbs. Black arrows indicate vwde expression, scale bar is 100 µm. (f) OrthoFinder 2.0 phylogeny with corresponding protein domain structure for putative Vwde orthologs. Protein domain pictures were generated with drawProteins (Brennan, 2018). Species and Uniprot ID or transcriptome contig number are included. Polypterus vwde contained multiple splice isoforms and the closest match to axolotl Vwde is shown here. Axolotl Vwde is denoted with “*” and other species Vwde that are described in this manuscript are marked with “#.” Orthologs to the Vwde studied in this study are indicated with brackets, paralog is also denoted with brackets. FPKM, fragments per kilobase of exon mapped [Color figure can be viewed at wileyonlinelibrary.com]|
|Figure 3. vwde expression is tightly linked with the regeneration‐competent environment. In situ hybridization chain reaction probing for vwde in (a–f) regeneration‐competent Xenopus laevis tails (a,b) before amputation, (c,d) blastema 24 hr postamputation, and (e,f) the peripheral edge of the amputation plane 24 hr postamputation. (g–l) Regeneration‐refractory tails (g,h) before amputation, (i,j) blastema 24 hr postamputation, and (k,l) the peripheral edge of the amputation plane 24 hr postamputation. White arrows indicate the location of vwde expression. Scale bars = 100 µm. DAPI, 4′,6‐diamidino‐2‐phenylindole [Color figure can be viewed at wileyonlinelibrary.com]|
References [+] :
, UniProt: a worldwide hub of protein knowledge. 2020, Pubmed