Suppressive effects of valproic acid on caudal fin regeneration in adult zebrafish

Abstract

Zebrafish can regenerate fins following injury through an epimorphic process that includes the formation of new tissues and reconstruction of the original morphology. In this study, the effects of valproic acid (VPA), a widely used anti-epileptic drug, on fin regeneration were studied after the caudal fin amputation of adult zebrafish. In the control group, zebrafish formed new tissues and reconstructed the original rays 14 days after amputation (dpa). Meanwhile, VPA treatments between 20 and 200 µM following amputation suppressed fin regeneration in a dose-dependent manner and altered morphological characteristics, such as bifurcation and segmentation, in the rays. Compared to the control, VPA also delayed blastema formation and decreased cell proliferation in the mesenchymal area of the regenerated fin. The mRNA expression of lef1, a downstream signaling gene in the Wnt pathway, was transiently increased in the regenerated fin of the control at 2 dpa; the same increase was not observed in the VPA-treated zebrafish. Sodium butyrate (SB), an histone deacetylase activity (HDAC) inhibitor, suppressed the fin regeneration without affecting the morphological characteristics of the regenerated ray. Furthermore, the transient increase of lef1 mRNA was not suppressed in the SB-treated zebrafish. These results suggested that VPA's suppressive effects on fin regeneration are partly mediated through decreased cell proliferation and lef1 mRNA expression.

Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

“…There are several hypotheses on how VPA causes NTDs, including alterations in folate metabolism, increase in reactive oxygen species, and epigenetic dysregulation ( 30 - 34 ). For instance, the effect of VPA as a folic acid antagonist is primarily supported by a comparative analysis between the effects of methotrexate and VPA ( 35 - 37 ).…”

The Expression and Function of lincRNA-154324 and the Adjoining Protein-Coding Gene vmp1 in the Caudal Fin Regeneration of Zebrafish

“…Zebrafish caudal fins are widely used in tissue regeneration research because of their strong regenerative ability and the existence of similar gene regulation pathways in humans [ 29 ]. Caudal fin regeneration is an extremely complex process in which a variety of molecular and biological phenomena, such as cell proliferation, apoptosis, migration, and differentiation, are involved [ 30 , 31 , 32 , 33 ]. This process is precisely regulated by a variety of gene regulatory networks and multiple signaling pathways.…”

egfl6 expression in the pharyngeal pouch is dispensable for craniofacial development

“…Fluorescent in situ hybridizations in conjunction with GFP immunohistochemistry (NC9589665, Torrey Pines Biolabs, 1:1000), Alcama/ZN8 immunohistochemistry (AB_531,904, Zebrafish International Resource Center, 1:400), and Alcian Blue staining were performed as described previously (Crump et al 2004a ; Zuniga et al 2011 ; Lee et al 2020 ; Chowdhury et al 2021 ). Partial cDNA fragments of egfl6 , egfl7 , and rag1 were amplified from mixed-stage embryos and cloned into the pGEM ® -T easy vector (A1360, Promega).…”