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Title: Apical process retraction upon neurogenesis in the zebrafish retina
Author: Harris, W.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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When neurons exit the cell cycle after division at the apical surface of the proliferating neuroepithelium, they sever their attachments to the apical surface while migrating to their correct laminar positions. Although apical retraction is an essential step in neuronal differentiation, its underlying molecular mechanisms remain unknown. The accessibility of the retina, together with the ease of genetic manipulation and in vivo imaging capabilities of the vertebrate zebrafish, make zebrafish retinal ganglion cells (RGCs) an ideal model system to study the molecular basis of apical retraction in the CNS. I was able to show that the axonal guidance molecule, Slit1b, is necessary for apical retraction. Slit1b mRNA is expressed during RGC differentiation. Time-lapse imaging in slit1b morphants revealed a delayed retraction of apical processes in RGCs. Other developmental events, such as axon extension, progresses normally, thus ruling out a general developmental delay. Transcripts of the Slit receptors, robo2 and robo3, were detected in the retina during RGC differentiation. Morpholino knockdown experiments revealed that robo3, but not robo2, was required for normal apical retraction of RGCs. In addition, expression of dominant-negative N-cadherin caused RGCs to lose apical attachments prematurely. Finally, dominant-negative N-cadherin expression in slit1b morphants resulted in early retraction even in slit1b morphants, suggesting that N-cadherin functions downstream of Slit/Robo signalling during apical retraction. This study helped shed light on molecular events underlying apical retraction in RGCs. It now needs to be shown if these mechanisms are more general during neuronal differentiation throughout the CNS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available