Cell-cell signalling molecules play important roles in neural development. In response to extracellular signals, neuronal progenitor cells proliferate, differentiate, and form a neuronal network. In the vertebrate retina, retinal ganglion cells (RGCs) are the first neurons produced during development and are the only neurons that send projections to the brain. However, the molecular mechanisms for RGC development have not been fully understood. In this study, I have investigated the expression and functions of Nel (Neural Epidermal Growth Factor Like), an extracellular glycoprotein that contains chordin-like domains and epidermal growth factor-like domains, in the development of the chick RGCs and retinotectal projection. I found that on embryonic days (E) 2-3.5, Nel was expressed in the presumptive retinal pigment epithelium of the developing eye. Correspondingly, Nel-binding activity (Nel receptor activity) was detected in the retinal pigment epithelium and also the progenitor layer of the neural retina. At the early stages during RGC formation, Nel overexpression increased the total number of RGCs and accelerated the progression of RGC differentiation wave. Conversely, Nel expression knockdown decreased the total number of RGCs and slowed down the progression of RGC differentiation wave. At later stages (E3-E18), expression of Nel in the retina was in the retinal pigment epithelium and the RGC layer, whereas receptor activity for Nel was localized in the retinal pigment epithelium and the RGC axons. In vivo, Nel overexpression in the developing retina induced the inhibition of RGC axons and thus disrupting the intraretinal RGC axon projection. These results suggest that Nel can positively regulate the production of RGCs at the early stages during retinal development, and at the later stages, Nel can function as an inhibitory guidance cue in vivo for RGC axons.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:569604 |
| Date | January 2012 |
| Creators | Kuan, Soh Leh |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192183 |
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