The aim of my research was to understand how RPTPs are involved in retinal ganglion cell (RGC) axon outgrowth and guidance in the development of the <I>Xenopus </I>visual system. I first describe the cloning and expression patterns of a variety of RPTPs in the developing <I>Xenopus</I> embryo, focusing on the retinotectal system. All three members of Type IIa RPTPs; LAR, PTP-δ, and CRYP-α, are expressed in RGCs during periods of differentiation, axonogenesis, and axon guidance from the retina to the tectum. These three RPTPs, as well as PTP-p, are expressed in overlapping but distinct patterns in the developing <I>Xenopus</I> embryo. Expression patterns of putative ligands for CRYP-α and LAR were examined using receptor affinity probe in situ hybridisation in the developing retina and brain, and putative ligands for CRYP-α were found along the optic pathway and in the tectum. These results demonstrate that Type IIa RPTPs and their putative ligands are expressed in a spatial and temporal pattern consistent with their involvement in RGC axon guidance and outgrowth from the retina to the tectum. I also describe functional studies examining the role of RPTPs in the developing <I>Xenopus</I> visual system both in vitro and in vivo. In vitro analysis of RGCs expressing dominant negative RPTPs demonstrates that dominant negative PTP-δ inhibits RGC axon outgrowth, while dominant negative CRYP-α promotes outgrowth, in a substrate-dependent manner. In vivo analysis of RGC axon outgrowth and guidance demonstrates that although dominant negative PTP-δ and LAR reduce the rate of axon outgrowth, none of these RPTPs appear to be involved in axon guidance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:605647 |
| Date | January 2000 |
| Creators | Johnson, K. G. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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