Item – Theses Canada

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OCLC number
758060695
Link(s) to full text
LAC copy
LAC copy
Author
Atkinson-Leadbeater, Karen P.(Karen Paige),1975-
Title
The role of fibroblast growth factors in visual system development.
Degree
Ph. D. -- University of Calgary, 2010
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2011]
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
In this thesis I explored two key roles for the fibroblast growth factor (FGF) family of proteins in visual system development in the frog, ' Xenopus laevis'. First, in early development, FGFs act as classical patterning molecules to regulate the normal expression of 'xlhx9' within the retinal primordium. Interestingly, FGF regulation of 'xlhx9 ' is under tight temporal control: between stages 12 and 16 of ' Xenopus' embryonic development (a five-hour span) FGFs are required for normal 'xlhx9' expression within the retina, however, beyond stage 16, retinal 'xlhx9' expression is maintained independently of FGF signalling. Inhibition of FGF signalling for five hours between stages 12 and 16 also gave rise to embryos lacking ventral retinal tissue, suggesting that this early role regulating gene expression in the eye primordium has long-term consequences for retinal development. In the second instance, I discovered a novel role for FGFs much later in development, after the nervous system has been extensively patterned. Here, FGF signalling is necessary to maintain the expression of two cues, ' xslit1' and 'xsema3A', that guide the developing axons of retinal ganglion cells (RGCs) from the retina to their midbrain target. With diminished FGF signalling, RGC axons were unable to navigate beyond a stereotypic turn in the forebrain and therefore failed to reach their midbrain target. Interestingly, inhibition of FGF signalling also resulted in decreased levels of 'xslit1' and 'xsema3A', two proteins known to guide developing axons. Importantly, RGC axons also failed to navigate beyond the midbrain after targeted downregulation of 'xslit1' and 'xsema3A' levels, which argues that FGFs promote normal RGC axon development by maintaining the expression of 'xsema3A' and 'xslit1'. Therefore, FGFs act at both early and late stages of visual system development by regulating gene expression. These data suggest that secreted patterning molecules play iterative roles throughout development: they continue to signal to neighbouring cells to promote normal gene expression, however, they do so in an increasingly restricted manner.
ISBN
9780494621349
0494621346