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The role of the zebrafish unplugged ...

Zhang, Jing.

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The role of the zebrafish unplugged gene in motor axon pathfinding.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The role of the zebrafish unplugged gene in motor axon pathfinding./
Author:	Zhang, Jing.
Description:	217 p.
Notes:	Source: Dissertation Abstracts International, Volume: 62-05, Section: B, page: 2154.
Contained By:	Dissertation Abstracts International62-05B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3015397
ISBN:	0493257632

The role of the zebrafish unplugged gene in motor axon pathfinding.
Zhang, Jing.

The role of the zebrafish unplugged gene in motor axon pathfinding. - 217 p.

Source: Dissertation Abstracts International, Volume: 62-05, Section: B, page: 2154.

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

During embryonic development, motor axons navigate long distances through a complex environment to form precise connections with their target muscles. This accurate pathfinding process is facilitated by specialized cells scattered along motor axon pathways. These specialized cells, serving as intermediate targets or choice points, provide molecular guidance cues that instruct all motor growth cones to enter and migrate on a common path as well as cues that control individual population of motor growth cones to select divergent pathways. Previous studies in invertebrates and vertebrates have identified numerous genes involved in motor axon guidance. However, the molecular identities of guidance cues remain largely elusive. To identify the guidance cues controlling motor axon pathway selection, I used well-characterized zebrafish primary motor neurons as a model system. I show that in the <italic>unplugged</italic> mutants of zebrafish, pathway selections of two primary motor neurons, RoP and CaP, are specifically affected. Analyses of chimeric embryos demonstrate that the <italic>unplugged</italic> gene acts cell non-autonomously for motor axon guidance and the guidance defect can be rescued by a subgroup of wild-type derived adaxial cells. These cells are located dorsal to the choice point and influence pathway selection of motor axons through a contact-independent mechanism. Thus, the <italic>unplugged</italic> gene may encode a guidance cue controlling motor axon pathway selection. Furthermore, I examined the axonal trajectories of secondary motor neurons in <italic>unplugged</italic> mutants. Secondary motor axons display similar, but not identical, defects as primary motor axons. Due to the novel phenotype of <italic>unplugged</italic> mutants, there is no good candidate for the mutated gene. Therefore, I undertook a positional cloning approach to identify the <italic>unplugged</italic> locus, <italic> unplugged</italic> maps to the centromere of LG 10. I tested 9,380 meioses to generate a high-resolution map around the <italic>unplugged</italic> locus. To date, I have covered part of the critical interval of the <italic>unplugged </italic> locus with BAC/PAC clones. Systematic isolation of transcription units in the critical region and test of their candidacy for the <italic> unplugged</italic> gene are underway. These efforts provide a foundation for future studies aiming at identification of the <italic>unplugged</italic> gene and investigation of its mechanism in motor axon guidance.

ISBN: 0493257632Subjects--Topical Terms:

1017686
Biology, Cell.

The role of the zebrafish unplugged gene in motor axon pathfinding.
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020 $a 0493257632
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035 $a AAI3015397
040 $a UnM $c UnM
100 1 $a Zhang, Jing. $3 846303
245 1 0 $a The role of the zebrafish unplugged gene in motor axon pathfinding.
300 $a 217 p.
500 $a Source: Dissertation Abstracts International, Volume: 62-05, Section: B, page: 2154.
500 $a Supervisor: Michael Granato.
502 $a Thesis (Ph.D.)--University of Pennsylvania, 2001.
520 $a During embryonic development, motor axons navigate long distances through a complex environment to form precise connections with their target muscles. This accurate pathfinding process is facilitated by specialized cells scattered along motor axon pathways. These specialized cells, serving as intermediate targets or choice points, provide molecular guidance cues that instruct all motor growth cones to enter and migrate on a common path as well as cues that control individual population of motor growth cones to select divergent pathways. Previous studies in invertebrates and vertebrates have identified numerous genes involved in motor axon guidance. However, the molecular identities of guidance cues remain largely elusive. To identify the guidance cues controlling motor axon pathway selection, I used well-characterized zebrafish primary motor neurons as a model system. I show that in the <italic>unplugged</italic> mutants of zebrafish, pathway selections of two primary motor neurons, RoP and CaP, are specifically affected. Analyses of chimeric embryos demonstrate that the <italic>unplugged</italic> gene acts cell non-autonomously for motor axon guidance and the guidance defect can be rescued by a subgroup of wild-type derived adaxial cells. These cells are located dorsal to the choice point and influence pathway selection of motor axons through a contact-independent mechanism. Thus, the <italic>unplugged</italic> gene may encode a guidance cue controlling motor axon pathway selection. Furthermore, I examined the axonal trajectories of secondary motor neurons in <italic>unplugged</italic> mutants. Secondary motor axons display similar, but not identical, defects as primary motor axons. Due to the novel phenotype of <italic>unplugged</italic> mutants, there is no good candidate for the mutated gene. Therefore, I undertook a positional cloning approach to identify the <italic>unplugged</italic> locus, <italic> unplugged</italic> maps to the centromere of LG 10. I tested 9,380 meioses to generate a high-resolution map around the <italic>unplugged</italic> locus. To date, I have covered part of the critical interval of the <italic>unplugged </italic> locus with BAC/PAC clones. Systematic isolation of transcription units in the critical region and test of their candidacy for the <italic> unplugged</italic> gene are underway. These efforts provide a foundation for future studies aiming at identification of the <italic>unplugged</italic> gene and investigation of its mechanism in motor axon guidance.
590 $a School code: 0175.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Neuroscience. $3 1017680
690 $a 0379
690 $a 0307
690 $a 0317
710 2 0 $a University of Pennsylvania. $3 1017401
773 0 $t Dissertation Abstracts International $g 62-05B.
790 1 0 $a Granato, Michael, $e advisor
790 $a 0175
791 $a Ph.D.
792 $a 2001
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3015397