What Xenopus fibrillin does in the early embryo; clues from a dominant negative approach
The developing frog, like any vertebrate, undergoes a startling transformation during gastrulation. This morphogenesis transforms it from a hollow ball of cells into a tadpole. Yet little is known about the molecular interactions that drive this process. The position specific cellular behaviors that...
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| Format: | Dissertation |
| Language: | English |
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ProQuest Dissertations & Theses
01-01-1996
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| Online Access: | Get full text |
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| Summary: | The developing frog, like any vertebrate, undergoes a startling transformation during gastrulation. This morphogenesis transforms it from a hollow ball of cells into a tadpole. Yet little is known about the molecular interactions that drive this process. The position specific cellular behaviors that occur at gastrulation have been extensively studied and a part of the embryo, the Dorsal Involuting Marginal Zone (DIMZ), has been identified as mechanically organizing blastopore closure and axial exension. This tissue, a component of Spemann's Organizer that generates dorsal mesoderm, accomplishes this by expressing a stereotypical series of cellular behaviors collectively called Mediolateral Intercalation Behavior (MIB) to drive convergent extension and generate directed force. These behaviors are induced and organized spatially and temporally in the involuting mesoderm and follow the notochordal-somitic boundary as it develops, suggesting that this boundary helps to pattern these cellular behaviors. This work describes the isolation a Xenopus fibrillin homolog, the onset of its expression in the DIMZ as it involutes, and the localization of Xenopus fibrillin protein to the developing notochord-somite boundaries. The Human fibrillins are associated with the autosomal dominant diseases Marfan Syndrome and Congenetal Contractural Arachnodactyly, and some alleles have been shown to act in a dominant negative fashion on wild type Injection of a Xenopus mimic of these alleles ($\Delta$XF) into the DIMZ of developing embryos causes gastrulation arrest, implicating the native Xenopus Fibrillin in convergent extension of the DIMZ in these "Marfan frogs". Explants of DIMZ (Keller explants) can autonomously extend in culture. Expression of $\Delta$XF unilaterally in such extending explants perturbs localization of native Xenopus fibrillin to the notochord-somite boundary, consistent with a dominant negative interpretation of its action. In addition, this expression causes bending of the extending explant towards the side of injection, consistent with a reduction in force of extension on this side. Since the boundary serves as a mechanical integrator of MIB for extension, disrupting it may be the basis for reduced force of extension. In addition, individual cells that express $\Delta$XF fail to undergo MIB, providing an alternate, cellular, explanation for a reduction in force of extension. |
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| ISBN: | 9780591075526 0591075520 |