Thyroid hormone-informed patterning and remembered positional identity direct zebrafish fin ray morphology

Abstract

Resolving the mechanisms that orchestrate patterning in complex tissues – particularly how positional identity is instantiated, remembered, and directed – is imperative to understanding the morphogenesis of appendages. The zebrafish (Danio rerio) caudal fin skeleton is a powerful model to investigate these questions, as its precisely patterned bony fin rays are restored through regeneration. My aims in this thesis were to investigate the role of endocrine metabolic regulator thyroid hormone (TH) signaling during fin ray morphogenesis and how spatial identity is retained and redeployed during regeneration. I began my work by resolving TH signaling effects on the fin skeleton. Through nuclear receptor Thrab, TH acutely induces distal features in both development and regeneration (Chapter 2). To better understand how distal features are remembered, I established novel microsurgery techniques that would discriminate autonomous versus environmental components of ray patterning. While the rate of regeneration does appear to retain positional memory, I found ray patterning is instead informed by extrinsic cues (Chapter 3). During my investigation of TH activity in Chapter 2, I noted robust TH signaling in peripheral rays. Repurposing the microsurgeries developed in Chapter 3, I discovered this TH signaling is an inherent feature of peripheral rays, and this activity regulates local Notch pathway signaling (Chapter 4). My research has revealed many mechanisms—both dependent and independent of TH—that regulate fin ray patterning and how this positional identity is retained and redeployed during regeneration.