Electronic Thesis/Dissertation
TBX5 AND TBX15 MEDIATE ZEBRAFISH POSTERIOR LATERAL LINE DEVELOPMENT AND STRATEGIES FOR RNA INTERFERENCE IN ZEBRAFISH Open Access
The zebrafish posterior lateral line (pLL) enables fish to sense movement in the aqueous environment. At 3 days post fertilization (dpf), the pLL consists of neuromasts arranged linearly along the horizontal myoseptum. Neuromasts possess a core of hair cells surrounded by supporting cells. Hair cells are the functional mechanosensory cells. Supporting cells maintain hair cells and are essential for regenerating damaged hair cells. pLL development is a dynamic process involving tissue patterning, migration and neuromast deposition, which are coordinated through balanced interaction of multiple signaling pathways. After development, the pLL remains dynamic. Damage to hair cells results in an immediate response to regenerate hair cells. The pLL developmental process and hair cell regeneration make the pLL relevant to several human physiological processes. Tissue patterning and migration are essential to the immune response and are involved in tumor metastasis. Hair cell regeneration is interesting because human hair cells do not regenerate, and damage causes permanent hearing loss. Thus, study of this organ in zebrafish has the potential to provide multiple clinical benefits. T-box transcription factors are implicated in many developmental processes. tbx5 and tbx15 have emerged as targets for investigation following expression profiling, and their roles in pLL development were examined. Tbx5 is an upstream activator of several genes expressed within the primordium and functions in establishing gene expression patterns in the primordium. One of these downstream targets, camk2b2, is also important in pLL development and impacts signaling molecule expression. Furthermore, Camk2b2 activates tbx15, which modulates tbx5 expression. Thus, tbx5, tbx15 and camk2b2 set up a negative feedback loop, resulting in carefully balanced Tbx5 and Camk2b2 activity. Methodologies for RNA interference (RNAi) in zebrafish to enable spatio-temporal control of gene expression have also been investigated. These systems are important in studies of hair cell regeneration, as they enable study of the regenerative process after normal development has occurred. This goal is important because regeneration and development are regulated by many of the same genes. Thus, novel roles for tbx5 and tbx15 in pLL development have been identified, and efforts are underway to develop mechanisms for study of hair cell regeneration.
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Whitehurst_gwu_0075A_10754.pdf | 2018-01-15 | Open Access |
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