Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration

Abstract

During appendage regeneration in urodeles and teleosts, tissue replacement is precisely regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly established after amputation, a dynamic gradient of positional information along the proximodistal (PD) axis of the appendage that assigns region-specific instructions to injured tissue. These instructions specify the amount of tissue to regenerate, as well as the rate at which regenerative growth is to occur. A striking theme among many species is that the rate of regeneration is more rapid in proximally amputated appendages compared with distal amputations. However, the underlying molecular regulation is unclear. Here, we identify position-dependent differences in the rate of growth during zebrafish caudal fin regeneration. These growth rates correlate with position-dependent differences in blastemal length, mitotic index and expression of the Fgf target genes mkp3, sef and spry4. To address whether PD differences in amounts of Fgf signaling are responsible for position-dependent blastemal function, we have generated transgenic fish in which Fgf receptor activity can be experimentally manipulated. We find that the level of Fgf signaling exhibits strict control over target gene expression, blastemal proliferation and regenerative growth rate. Our results demonstrate that Fgf signaling defines position-dependent blastemal properties and growth rates for the regenerating zebrafish appendage.

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

“…The transgenic method combined with the heat inducible promoter hsp70 (HS) is a powerful tool to manipulate specific pathways at a specific time during the regeneration process. It has been used many times in Xenopus and zebrafish to dissect a specific molecular pathway used during regeneration (see Section 2.2; Beck et al, 2003Beck et al, , 2006Lee et al, 2005;Stoick-Cooper et al, 2007b;Yokoyama et al, 2007;Lin and Slack, 2008). To direct the spatial action of a protein more precisely, beads soaked in recombinant protein solution or cell aggregates expressing a specific protein have been grafted into the amputation stump Satoh et al, 2005a;Sugiura et al, 2008) and virus infection has also been used (Kawakami et al, 2006).…”

Tissue regeneration after injury in adult zebrafish: The regenerative potential of the caudal fin

“…Fin regeneration is a particularly efficient model for studying tissue regeneration. Although the fins may vary in shape, length, and color, they are built by identical skeletal elements (Becerra et al, 1983;Geraudie et al, 1995;Bennett, 1999, Kawakami et al, 2004;Lee et al, 2005;Murciano et al, 2007;Huang et al, 2009;Kizil et al, 2009). In response to injury, major fin structures may regenerate very rapidly in zebrafish.…”

Dually inducible TetON systems for tissue-specific conditional gene expression in zebrafish

“…Currently, two technologies for conditional overexpression are being regularly used in zebrafish. Heat-shock promoter-driven overexpression works well in embryos and has been successfully used to study gene function during adult regeneration and homeostasis (4,5). Although this is a robust method that appears to work in almost all cell types, its usefulness is severely limited by lack of spatial control and the pulsed nature of expression.…”