Luehders, KA;
(2016)
The role of small leucine-rich repeat proteoglycan Asporin in early eye development.
Doctoral thesis , UCL (University College London).
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Abstract
There has been a longstanding research interest in understanding the exact mechanisms underlying the correct development of the eye, with the goal of treating eye disease and blindness. While there have been enormous advances in the field of regenerative medicine, there is still some way to go before these advances can be translated into clinical applications. Very little is currently known about the regulatory mechanisms controlling the very early stages of eye development. While the genes, which regulate eye field development have been well characterised, their induction and mechanism of action, including downstream signalling targets and associated downstream signalling systems, still largely remain to be elucidated. The small leucine-rich repeat proteoglycan (SLRP) family of proteins play important roles in a number of biological events, such as proliferation, growth and differentiation. Class I SLRP Asporin (ASPN) has so far been mainly associated with research relating to cartilage homeostasis, osteoarthritis susceptibility and more recently cancer. In this study, I introduce ASPN as a new important factor in Xenopus laevis early eye development. During frog embryogenesis, ASPN is broadly expressed in the neuroectoderm of the embryo. The overexpression of ASPN causes the induction of ectopic eyes. In contrast, blocking ASPN function with morpholino-oligonucleotides inhibits eye formation, indicating that ASPN is an essential factor for eye development. Detailed molecular analyses revealed that ASPN interacts with insulin growth factor receptor (IGF1R) and is essential for activating the IGF-receptor mediated intracellular signalling pathway. Furthermore, ASPN perturbed the Wnt, BMP, and Activin signalling pathways, suggesting that ASPN thereby creates a favourable environment in which the IGF signal can dominate. ASPN is thus a novel secreted molecule critical for eye induction through the coordination of multiple signalling pathways.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The role of small leucine-rich repeat proteoglycan Asporin in early eye development |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Keywords: | ASPN, Xenopus, eye induction, IGF, anterior-posterior polarity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1501163 |
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