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Updated: Jun 11, 2026
Functional Manipulation of Maternal Gene Products Using In Vitro Oocyte Maturation in Zebrafish
Published on: April 22, 2017
Zebrafish ProVEGF-C expression, proteolytic processing and inhibitory effect of unprocessed ProVEGF-C during fin
Abdel-Majid Khatib1, Rachid Lahlil, Nathalie Scamuffa
1INSERM, UMRS940, Equipe Avenir. Institut de Génétique Moléculaire, Hôpital St-Louis, Université Paris 7, Paris, France.
Background:
In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration.
Methodology/Principal Findings:
Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR(214) into HSIISS(214)). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 4-7 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration.
Conclusions/Significances:
Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration.
