Date

9-2013

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Functionality of the vertebrate sensory system depends on coordinated development of the signal-transmitting cells called neurons and their sensory organ targets. Neuronal cells undergo dynamic changes in architecture in order to form the unique, polarized structures characteristic of neurons: axons and dendrites. In sensory systems, the sensory structures that neurons innervate also undergo dramatic changes in cell shape in order to form the proper adult sensory organs. Together, these developmental changes in cell characteristics are critical for proper adult sensory perception. However, the complete complement of molecular cues and pathways required for these morphological changes have not been fully elucidated. During embryonic development, apical constriction drives cell shape changes important for diverse developmental processes, including gastrulation and neural tube closure (Sawyer et al., 2010). This cellular behavior is characterized by the narrowing of the apical domain of an initially columnar cell. Typically, this process is dependent on contraction of an acto-myosin network. However, the extracellular signals that drive this behavior in multiple contexts are not well understood. In this work, we ask how extracellular signals regulate apical constriction during development of the zebrafish posterior lateral line (pLL), a mechanosensory organ system. Formation of the pLL is reliant upon establishment of transient structures called rosettes that are formed through apical constriction. Rosettes will ultimately be deposited along the embryonic trunk and differentiate into mechanosensory organs called neuromasts (NMs). In 1 this work, we define a novel role for the extracellular signaling molecule Fibroblast Growth Factor (Fgf) in controlling apical constriction through Rhokinase 2a (Chapter 1). Concurrent with development of pLL mechanosensory organs, afferent axons extend to innervate nascent NMs. The cell bodies of these very long axons reside behind the ear in the posterior lateral line ganglion (pLLg). Proper outgrowth of pLLg axons depends on function of the receptor tyrosine kinase Ret and its ligand GDNF. Here, we show that proper localization of Ret in the growth cones of extending axons is dependent of the scaffolding molecule JNKinteracting protein 3 (Jip3). Using a zebrafish mutant for Jip3, we show that Jip3 is required for proper transport of Ret, and in the absence of Jip3, Ret accumulates in the growth cones and axons fail to completely extend (Chapter 2). A complete understanding of the processes that drive vertebrate organ development is critical for improving treatment of developmental disorders for human patients. Together, the studies presented here reveal how molecular signals drive changes in cell shape. The two models for cell shape change studied here, the neurons and sensory cells of the zebrafish posterior lateral line, are complementary and distinct in terms of the signals required for proper morphogenesis. We show that deregulation of these molecules and signals cause improper formation of sensory organ systems.

Identifier

doi:10.6083/M4VH5M4W

Division

Neuroscience Graduate Program

School

School of Medicine

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