Leong, Li Ming; (1996) The role of bone morphogenetic protein-4 in the developing chick eye. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Bone morphogenetic protein-4 (Bmp-4) is a member of the Transforming Growth Factor-β (TGF-β) superfamily of secreted signalling molecules. In this work, I have investigated its spatiotemporal distribution and possible function in the developing chick eye. The chick homologue of Bmp-4 is expressed throughout the developing chicken optic vesicle between Hamburger and Hamilton stages 13 and 17. It then shows a distinctive restriction to the dorsal quadrant of the eye until stage 30, when expression begins to fade, becoming undetectable by stage 35. Transcripts of the homeobox-containing gene GH6 show a similar dorsal restriction to Bmp-4, but between stages 20-35. Overexpression of Bmp-4 in vivo results in no detectable change in eye morphology, but enlarges the expression domain of GH6, indicating that the two genes may form part of a gene cascade involved in patterning the eye. In vitro, BMP-4 appears to stimulate retinal cell proliferation. It has no effect on retinal cell differentiation in vitro. In the chick, the patterning activities of sonic hedgehog (shh) are known to involve activation of Bmp expression in at least two instances; the development of the limb and midgut. I report here that shh is not expressed in the chick eye at all during development, but is found in the ventral portion of the diencephalon (forebrain). The available data suggests a number of roles for BMP-4 in chick eye development. BMP-4 may specify dorso-ventral retinal polarity required for proper retinal axon pathfinding, or establish a dorso-ventral gradient of cell proliferation in the developing optic cup. Alternatively, it may act as a hedgehog family member antagonist in establishing the retinal identity of the most dorsal portion of the eyecup.

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