FGF Regulation of Zebrafish Lateral Line Development

University Of Washington, Seattle WA

Investigators

Abstract

Abstract Mechanisms that regulate developmental processes during organogenesis are complex. The zebrafish lateral line is an excellent system to study these processes since it is easily accessible for observation and manipulation. Sensory hair cells of the lateral line are positioned on the surface of the body to detect flow of water. Hair cells are deposited along the body by a migrating cluster of about 100 cells called the primordium that originates from a cranial placode. This proposal will test the roles of Fibroblast Growth Factors (Fgfs) in lateral line development, through genetic and embryological manipulation. Preliminary data reveal that Fgf signaling is critical for lateral line patterning. In Aim 1, the expression of Fgfs and Fgf signaling components within the lateral line will be carefully documented. In Aim 2, the roles of Fgf in the migration of the lateral line primordium will be explored. Using a transgenic line where Fgf signaling is conditionally inactivated by expression of a truncated Fgf receptor, the time and location of required Fgf signaling will be determined. In Aim 3, the effects of blocking Fgf10 on migration, patterning and proliferation will be documented. Antisense morpholino oligonucleotides will be introduced into embryos to characterize the role of Fgf 10 on neuromast deposition. The combined roles of Fgf10 with Fgf3 will also be examined. The proposed studies examining the roles of Fgf signaling in lateral line development have the opportunity to reveal fundamental mechanisms underlying coordination of cell proliferation, migration and differentiation during embryogenesis. The proposed studies may shed light on the similar roles of Fgf signaling in regulating migration and proliferation during angiogenesis and tumorigenesis. There is significant variation amongst aquatic vertebrates in the patterning of the lateral line organs, and defining molecular mechanisms that regulate patterning will allow future study that may determine factors that influence this variation. Understanding the mechanisms that regulate lateral line development may also reveal similarities with the development of other placode-derived structures including the auditory and vestibular organs.