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Title: The role of fibroblast growth factors in embryonic limb development
Author: Vogel, Astrid
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1995
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This thesis examines the role of Fibroblast growth factors (FGFs) during embryonic limb development. It appears that Fibroblast Growth Factors are central to signalling in the developing limb. The apical ectodermal ridge is a specialised epithelial structure at the tip of the limb bud and is involved in a major set of epithelial-mesenchymal interactions. Local FGF-4 application to the posterior margin of the bud in the absence of the ridge maintains posterior mesenchyme. These posterior cells constitute the polarizing region that mediates patterning across the limb. A generation of a full set of proximo- distal structures is correlated with maintenance of polarizing activity. FGFs can maintain the activity of polarizing region cells in vitvo and can also maintain responsiveness of cultured anterior cells to positional cues within the limb when grafted back to the posterior margin of a chick wing bud. FGFs also allow development of skeletal structures when either the whole limb bud of young or the distal limb tip of older embryos is removed. Expression of homeobox- containing genes in the developing limb has been linked to outgrowth and positional cues within the limb. Msx-1, a gene related to the Drosophila msx-1, a gene is expressed at the tip of the young limb bud in a zone of rapidly dividing and undifferentiated cells, under the control of the apical ectodermal ridge. Bmp-2, a member of the transforming growth factor family, is expressed in the apical ectodermal ridge and in posterior mesenchyme of the developing limb bud. Gene members of the HoxD complex are expressed in overlapping domains across the limb bud and these patterns can be regulated by cooperation between the polarizing region and the apical ectodermal ridge. When the apical ectodermal ridge is removed, or when posterior cells are taken from the bud and placed in culture, expression of Msx-1, Hoxd-13 and Bmp-2 is not detectable in mesenchymal cells. Local FGF-k application maintains normal expression patterns of Msx-1, Bmp-2 and Hoxd-13 in the absence of the ridge. Furthermore, addition of FGF-2 to cultured posterior mesenchyme cells maintains expression of Msx-1 and Hoxd-13.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available