Caudal Fin Regeneration in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 298

Zebrafish have the remarkable capability to regenerate their heart muscle (Poss
et al., 2002; Raya et al., 2004), retina, optic nerve (Becker and Becker, 2002), liver
(Sadler et al., 2007), spinal cord (Becker et al., 2004), and sensory hair cells (Lopez-
Schier and Hudspeth, 2006). Understanding the molecular and genetic pathways
that coordinately function to accomplish regeneration in this model, may explain
whymammals fail to respond to tissue injurywith a regenerative response and to the
generation of therapeutic interventions designed to overcome limitations in mam-
malian regenerative abilities.
22.2 SIGNALING AND EPIMORPHIC REGENERATION
The central goal of regeneration research is to elucidate the molecular signaling
networks that coordinately function to promote regeneration. There has been sig-
nificant progress in identifying genes and signaling pathways that function during
early fin regeneration through the use of mutagenic screens, loss-of-function and gain-
of-function experiments, gene expression studies, and chemical genetic approaches.
Both FGF and Wnt signaling have emerged as two main signaling pathways that
regulate virtually all aspects of epimorphic fin regeneration. These signaling networks
have also been shown to be influential regulators of heart (Lepilina et al., 2006;
Stoick-Cooper et al., 2007b), retina (Del Rio-Tsonis et al., 1997; Osakada et al., 2007;
Petersen and Reddien, 2008), and skeletal muscle (Floss et al., 1997; Otto et al., 2008)
regeneration, and in the case of Wnt, liver (Monga et al., 2001; Goessling et al., 2009)
and sensory hair cell regeneration. The ability of cells to determine their position in
three dimensions is critical for the establishment of proper patterning during
regeneration (Stoick-Cooper et al., 2007a) and activin, hedgehog, and retinoic acid
signaling have all been implicated in regulating cellular patterning during epimorphic
regeneration (Ferretti and Geraudie, 1995; Quint et al., 2002). Ultimately, a better
understanding of the complexity of signaling events that choreograph epimorphic
regeneration will provide new avenues for comparative studies in mammalian models
with the hope of developing novel therapeutics to slow or prevent tissue loss from
aging, injury, and disease.
22.3 CAUDAL FIN ARCHITECTURE
Zebrafish caudal fins are complex structures that contain 16-18 lepidotrichia (fin rays)
connected by soft tissue interrays that lack skeletal elements. The fin rays are a series
of bony segments comprised of a pair of concave hemirays surrounded by amonolayer
of scleroblasts (bone secreting cells). The hemirays function to protect an intraray
core consisting of mesenchymal cells, blood vessels, nerves, melanocytes, and
fibroblasts. Mesenchymal compartmental components are also present in the interray
space. The entire multiray fin is covered by an epithelial cell layer. The fin displays an
indeterminate ontogenetic growth pattern meaning that fin growth occurs by the
gradual addition of bony ray segments to the distal tip of the fin.