Functional Analysis and Receptor Identification of Nobel Membrane Protein CUBL in Floor Plate

点击翻译按钮获取中文摘要

Writing an enormous number of neurons in highly precise pattern is essential for the formation of the complex architecture of vertebrate nervous system. The formation of neural network primarily depends on the ability of growth cone, a tip of the growing axon, to interpret environmental cues along the pathway to the target region. Recent discovery of extracellular signaling molecules which act as chemoattractive cue, Netrin, and chemorepulsive cue, Semaphorin, Ephrin, and Slit, and the receptors (DCC, Eph, Robo, Plexin, and Neuropilin) has lead us to understanding of basic aspects of molecular mechanism of network, although it is far from complete because of high degree of complexity of the nervous system.In the present study, I identified a novel membrane protein CUBL and chemokine SDF-1 as genes that are expressed in the floor plate during nervous system development and play a role in the axon guidance of PC axons and retinal axons.CUBL is a novel membrane protein that has CUB domain and LDL receptor repeat domain in the extracellular region. It is expressed in the floor plate of midbrain, hindbrain and subcommissural organ. I generated transgenic zebrafish line that carries transgene CUBL under the control of heat shock promoter. In this system the transgene can be expressed ectopically in all tissues in the fish upon heat shock. The heat induction of the transgene was verified by either in situ hybridization or GFP fluorescence. I found that heat induction of CUBL in whole embryo leads to misrouting of PC axons. This result suggests role of CUBL in axon guidance of PC axons.