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The role of mini fin/tolloid in dors...

Connors, Stephanie Anne.

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The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo./
Author:	Connors, Stephanie Anne.
Description:	141 p.
Notes:	Source: Dissertation Abstracts International, Volume: 62-02, Section: B, page: 0690.
Contained By:	Dissertation Abstracts International62-02B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3003612
ISBN:	049312828X

The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo.
Connors, Stephanie Anne.

The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo. - 141 p.

Source: Dissertation Abstracts International, Volume: 62-02, Section: B, page: 0690.

Thesis (Ph.D.)--University of Pennsylvania, 2001.

A conserved TGF-β signaling pathway is essential for the establishment of the dorsal-ventral axis in both vertebrates and invertebrates. The bone morphogenetic protein (BMP) subclass of TGF-β signaling molecules establishes nearly all ventral cell fates, whereas inhibitors of BMPs promote the formation of dorsal mesodermal and neurectodermal derivatives. One of these inhibitors, Chordin, is itself inhibited by the metalloprotease Tolloid, which cleaves Chordin to increase BMP activity. Here, I investigate the role of Tolloid in patterning the dorsal-ventral axis of the zebrafish embryo. Injection of <italic>tolloid</italic> mRNA into six zebrafish dorsalized mutants rescues only one of these mutants, <italic>mini fin</italic>. Chromosomal mapping, linkage, and cDNA sequence analysis of several <italic>mini fin</italic> alleles demonstrate that <italic>mini fin</italic> encodes the <italic>tolloid </italic> gene. Characterization of the <italic>mini fin</italic> mutant phenotype reveals that Tolloid/Mini fin activity is required for patterning ventral tissues of the tail. Chimeric analyses indicate that Tolloid/Mini fin activity is required in a cell non-autonomous manner in the ventral-marginal cells of the gastrula, or the derivatives of these cells. <italic>mini fin</italic> mutants first exhibit reduced expression of ventral markers at the end of gastrulation. To more closely examine the temporal requirement for Tolloid/Mini fin activity, homozygous <italic>mini fin</italic> mutants carrying a <italic> tolloid</italic> transgene under the control of the inducible <italic>hsp70 </italic> promoter were generated. Transgenic analyses indicate that Tolloid/Mini fin activity is first required at the end of gastrulation for the proper specification of ventral tail cell fates. Overexpression of the <italic>hsp-tolloid</italic> transgene at different time points of development demonstrates that Chordin is required both during and after gastrulation for proper patterning of the embryo. Based on all of these results taken together, we propose that Tolloid/Mini fin modifies the BMP activity gradient at the end of gastrulation, when the ventral-most marginal cells of the embryo are in close proximity to the dorsal Chordin-expressing cells. At this time, unimpeded Chordin may diffuse to the most ventral marginal regions and inhibit high BMP activity levels. In the presence of Tolloid/Mini fin, however, Chordin activity is negatively modulated through proteolytic cleavage, thereby increasing BMP signaling activity to allow proper patterning of the tail.

ISBN: 049312828XSubjects--Topical Terms:

1017719
Biology, Molecular.

The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo.
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245 1 0 $a The role of mini fin/tolloid in dorsal-ventral pattern formation of the zebrafish embryo.
300 $a 141 p.
500 $a Source: Dissertation Abstracts International, Volume: 62-02, Section: B, page: 0690.
500 $a Supervisor: Mary C. Mullins.
502 $a Thesis (Ph.D.)--University of Pennsylvania, 2001.
520 $a A conserved TGF-β signaling pathway is essential for the establishment of the dorsal-ventral axis in both vertebrates and invertebrates. The bone morphogenetic protein (BMP) subclass of TGF-β signaling molecules establishes nearly all ventral cell fates, whereas inhibitors of BMPs promote the formation of dorsal mesodermal and neurectodermal derivatives. One of these inhibitors, Chordin, is itself inhibited by the metalloprotease Tolloid, which cleaves Chordin to increase BMP activity. Here, I investigate the role of Tolloid in patterning the dorsal-ventral axis of the zebrafish embryo. Injection of <italic>tolloid</italic> mRNA into six zebrafish dorsalized mutants rescues only one of these mutants, <italic>mini fin</italic>. Chromosomal mapping, linkage, and cDNA sequence analysis of several <italic>mini fin</italic> alleles demonstrate that <italic>mini fin</italic> encodes the <italic>tolloid </italic> gene. Characterization of the <italic>mini fin</italic> mutant phenotype reveals that Tolloid/Mini fin activity is required for patterning ventral tissues of the tail. Chimeric analyses indicate that Tolloid/Mini fin activity is required in a cell non-autonomous manner in the ventral-marginal cells of the gastrula, or the derivatives of these cells. <italic>mini fin</italic> mutants first exhibit reduced expression of ventral markers at the end of gastrulation. To more closely examine the temporal requirement for Tolloid/Mini fin activity, homozygous <italic>mini fin</italic> mutants carrying a <italic> tolloid</italic> transgene under the control of the inducible <italic>hsp70 </italic> promoter were generated. Transgenic analyses indicate that Tolloid/Mini fin activity is first required at the end of gastrulation for the proper specification of ventral tail cell fates. Overexpression of the <italic>hsp-tolloid</italic> transgene at different time points of development demonstrates that Chordin is required both during and after gastrulation for proper patterning of the embryo. Based on all of these results taken together, we propose that Tolloid/Mini fin modifies the BMP activity gradient at the end of gastrulation, when the ventral-most marginal cells of the embryo are in close proximity to the dorsal Chordin-expressing cells. At this time, unimpeded Chordin may diffuse to the most ventral marginal regions and inhibit high BMP activity levels. In the presence of Tolloid/Mini fin, however, Chordin activity is negatively modulated through proteolytic cleavage, thereby increasing BMP signaling activity to allow proper patterning of the tail.
590 $a School code: 0175.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
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710 2 0 $a University of Pennsylvania. $3 1017401
773 0 $t Dissertation Abstracts International $g 62-02B.
790 1 0 $a Mullins, Mary C., $e advisor
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3003612