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osu1061302731.pdf (22.44 MB)
ETD Abstract Container
Abstract Header
Identification and functional analysis of Zebrafish orthologs of genes
Author Info
Challa, Anil Kumar
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1061302731
Abstract Details
Year and Degree
2003, Doctor of Philosophy, Ohio State University, Molecular Genetics.
Abstract
Cell motility and migration are integral to the complex mechanics of animal development, growth and maintenance. The precise and stereotypical orchestration of cell motility is controlled by a number of molecules, both within cells and in the extracellular environment. The phenomenon of axonal growth cone motility during neural circuit formation is a special case of cell movement, and has been studied extensively over the past several years. A number of receptor-ligand interactions have been described that regulate this process and one example involves the Roundabout (Robo) receptor and its extracellular, secreted ligand Slit. Both of these molecules are evolutionarily conserved from worms to humans and have been shown to play important roles in axon guidance. To gain a better understanding of Robo orthologs in vertebrates, we chose zebrafish as our model system for the many experimental advatages it offers. A PCR-based strategy was employed to find zebrafish orthologs of Robo. Two orthologs (
robo1
and
robo3
) were identified whose expression patterns in the nervous system and non-neural tissues suggested a role in axon guidance and cell motility. Further characterization of
robo3
unveiled the presence of two distinct isoforms (
robo3a
and
robo3b
). The two isoforms exhibited spatially and temporally dynamic gene expression patterns. Functional analysis of
robo3
isoforms using an antisense gene 'knock-down' strategy suggested that
robo3b
functions during gastrulation, whereas
robo3a
is required for motor axon pathfinding. This study uncovers a novel function of the Robo receptor family in cell movements during gastrulation, complementing an earlier study that suggests a role of zebrafish Slit orthologs in gastrulation. The implication of Robo-Slit signaling in cell movements during gastrulation underscores the conservation of molecular mechanisms in a variety of cell motility phenomena. Cell motility and migration are integral to the complex mechanics of animal development, growth and maintenance. The precise and stereotypical orchestration of cell motility is controlled by a number of molecules, both within cells and in the extracellular environment. The phenomenon of axonal growth cone motility during neural circuit formation is a special case of cell movement, and has been studied extensively over the past several years. A number of receptor-ligand interactions have been described that regulate this process and one example involves the Roundabout (Robo) receptor and its extracellular, secreted ligand Slit. Both of these molecules are evolutionarily conserved from worms to humans and have been shown to play important roles in axon guidance. To gain a better understanding of Robo orthologs in vertebrates, we chose zebrafish as our model system for the many experimental advatages it offers. A PCR-based strategy was employed to find zebrafish orthologs of Robo. Two orthologs (
robo1
and
robo3
) were identified whose expression patterns in the nervous system and non-neural tissues suggested a role in axon guidance and cell motility. Further characterization of
robo3
unveiled the presence of two distinct isoforms (
robo3a
and
robo3b
). The two isoforms exhibited spatially and temporally dynamic gene expression patterns. Functional analysis of
robo3
isoforms using an antisense gene 'knock-down' strategy suggested that
robo3b
functions during gastrulation, whereas
robo3a
is required for motor axon pathfinding. This study uncovers a novel function of the Robo receptor family in cell movements during gastrulation, complementing an earlier study that suggests a role of zebrafish Slit orthologs in gastrulation. The implication of Robo-Slit signaling in cell movements during gastrulation underscores the conservation of molecular mechanisms in a variety of cell motility phenomena.
Committee
Mark Seeger (Advisor)
Pages
119 p.
Keywords
Zebrafish
;
Roundabout
;
Slit
;
Axon Guidance
;
Gastrulation
;
Cell motility
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Citations
Challa, A. K. (2003).
Identification and functional analysis of Zebrafish orthologs of genes
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1061302731
APA Style (7th edition)
Challa, Anil Kumar.
Identification and functional analysis of Zebrafish orthologs of genes.
2003. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1061302731.
MLA Style (8th edition)
Challa, Anil Kumar. "Identification and functional analysis of Zebrafish orthologs of genes." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1061302731
Chicago Manual of Style (17th edition)
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Document number:
osu1061302731
Download Count:
510
Copyright Info
© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.