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Cellular and Molecular Mechanisms of Zebrafish Fin Regeneration

During fin regeneration, a blastema, a group of de-differentiated cells, forms
underneath the wound epidermis. As regeneration proceeds, cells leave the proximal
blastema and enter the differentiation zone. Adjacent to the differentiation zone, a subset
of cells in the basal epidermal layer (BEL) express sonic hedgehog a (shha). Cells that
come in contact with BEL differentiate into osteoblasts and joint cells, enabling the
formation of bone segments at the end of each fin ray. Generally, fin regeneration occurs
similarly in males and females. However, breeding tubercles (BT), keratinized epidermal
structures on the male pectoral fin, result in regenerative differences when compared to
females. In this thesis, three aspects of zebrafish fin regeneration were studied: 1) Cell
lineage tracing of shha-expressing cells in the caudal fin regenerate; 2) The differentiation
of joint cells and osteoblasts in the caudal fin regenerate; 3) Regeneration of pectoral fin
BTs. Studies on caudal fin regenerates suggest osteoblasts and joint cells originate from a
common cell lineage, but are committed to different cell fates. Joint cells follow a genetic
pathway in which evx1 occurs downstream or parallel to hoxa13a and upstream of pthrp1.
In the absence of Evx1, presumptive joint cells are committed to an osteoblast cell fate.
Furthermore, joint cells do not regenerate following laser cell ablation, suggesting joint
cell differentiation occurs only at specific intervals during osteoblast regeneration.
Collectively, these results suggest a mechanism for joint cell differentiation during caudal
fin regeneration. Studies on pectoral fins indicate androgens induce and estrogens inhibit
BT formation. BT regeneration in males and androgen-treated females follows the
initiation of revascularization, but occurs concomitantly with a novel second wave of
angiogenesis. The inhibition of angiogenesis in androgen-treated females prevents BT
formation. Altogether, these results suggest the growth and regeneration of BTs requires a
v
hormonal stimulus and the presence of an additional blood vessel network naturally found
in males. In conclusion, these studies have increased the overall knowledge of key aspects
of zebrafish fin regeneration. A gain in understanding zebrafish regeneration provides a
basis in which treatments can be developed to induce regeneration in species with limited
regenerative capabilities.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/35241
Date January 2016
CreatorsMcMillan, Stephanie
ContributorsAkimenko, Marie-Andrée
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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