ECM alterations in Fndc3a (Fibronectin Domain Containing Protein 3A) deficient zebrafish cause temporal fin development and regeneration defects

Abstract

Fin development and regeneration are complex biological processes that are highly relevant in teleost fish. They share genetic factors, signaling pathways and cellular properties to coordinate formation of regularly shaped extremities. Especially correct tissue structure defined by extracellular matrix (ECM) formation is essential. Gene expression and protein localization studies demonstrated expression of fndc3a (fibronectin domain containing protein3a) in both developing and regenerating caudal fins of zebrafish (Danio rerio). We established a hypomorphic fndc3a mutant line (fndc3awue1/wue1) via CRISPR/Cas9, exhibiting phenotypic malformations and changed gene expression patterns during early stages of median fin fold development. These developmental effects are mostly temporary, but result in a fraction of adults with permanent tail fin deformations. In addition, caudal fin regeneration in adult fndc3awue1/wue1 mutants is hampered by interference with actinotrichia formation and epidermal cell organization. Investigation of the ECM implies that loss of epidermal tissue structure is a common cause for both of the observed defects. Our results thereby provide a molecular link between these developmental processes and foreshadow Fndc3a as a novel temporal regulator of epidermal cell properties during extremity development and regeneration in zebrafish.

UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly

“…tp63 zebrafish morphants affect skin integrity by making the skin more prone to microbial infection 29 . fndc3a −/− zebrafish show broken actinotrichia, aberrant collagen localization and cellular defects in epidermal cells during caudal fin development 30 . It is possible that these genes function downstream of the SUMOylation pathway, leading to phenotypes that overlap the UBA2- related syndrome.…”

Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes

“…Heatmap clusters 2 and 3 contain genes that are significantly higher in fetal tenocytes compared to both adult and ESCtenocytes and include ADGRL3, which play a role in cell adhesion, and LURAP1L, which is involved in cell migration. FNDC3A is involved in extremity development and fin regeneration [90], but its role in mammalian limb development is still to be determined. Other genes in these clusters have no clear role in tendon development.…”

Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth

“…Thus, 13-times-more FND3A peptides were identified in the wild-type trophoblasts ( Figure 6 B) which could be an indicator for the involvement of FND3A proteins in modelling the extracellular matrix of trophoblasts. For example, in Fndc3a- deficient zebrafish, changes in the extracellular matrix occur with defects in the fin development and regeneration [ 48 ]. The FND3A protein contains nine fibronectin type III domains and is necessary for cell adhesion between spermatids and Sertoli cells, while functional FND3A deletion in mice led to sterility [ 49 ].…”