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Cell Biological Underpinnings of Unc...
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Nichols, Ev L.,
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Cell Biological Underpinnings of Unc-6/netrin-mediated Axon Guidance /
Record Type:
Electronic resources : Monograph/item
Title/Author:
Cell Biological Underpinnings of Unc-6/netrin-mediated Axon Guidance // Ev L Nichols.
Author:
Nichols, Ev L.,
Description:
1 electronic resource (138 pages)
Notes:
Source: Dissertations Abstracts International, Volume: 86-08, Section: B.
Contained By:
Dissertations Abstracts International86-08B.
Subject:
Mutation. -
Online resource:
https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31901317
ISBN:
9798311947350
Cell Biological Underpinnings of Unc-6/netrin-mediated Axon Guidance /
Nichols, Ev L.,
Cell Biological Underpinnings of Unc-6/netrin-mediated Axon Guidance /
Ev L Nichols. - 1 electronic resource (138 pages)
Source: Dissertations Abstracts International, Volume: 86-08, Section: B.
Neural development requires the precise organization of neuronal connections across space and time. These processes are governed by distinct and specialized molecules which guide extending axons to specific locations within a developing organism. One critical axon guidance molecule is UNC-6/Netrin which bifunctionally directs axon growth toward (i.e. attraction) or away (i.e. repulsion) from the UNC-6. While genetic experiments implicate many molecules in regulating UNC-6 attractive and repulsive signaling, detailed cell biological mechanisms of UNC-6-mediatd axon growth in an intact nervous system remain scarce. The work in this dissertation aims to address this gap by examining the cell and molecular bases of UNC-6 attraction and repulsion. Using cutting-edge time-lapse imaging in living C. elegansnervous systems, I first identify roles for both haptotactic and chemotactic growth during axon attraction. Visualizing the interaction between the growing axon tip and UNC-6 indicates the UNC-40/DCC receptor enriches UNC-6 at the leading edge to stimulate continuous growth. Second, I utilize structural insights from UNC-6 in complex with the UNC-5 receptor to test in vivoroles for heparin sulfate proteoglycans (HSPGs) in axon repulsion in C. elegans. Targeted genetic perturbations indicate that HSPGs amplify the repulsive signaling by UNC-6 and UNC-5. Together, these data provide a common foundation of cell biological principles that drive UNC-6 function through polarization of the growth cone and actin-driven protrusion at the leading edge. .
English
ISBN: 9798311947350Subjects--Topical Terms:
837917
Mutation.
Cell Biological Underpinnings of Unc-6/netrin-mediated Axon Guidance /
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Neural development requires the precise organization of neuronal connections across space and time. These processes are governed by distinct and specialized molecules which guide extending axons to specific locations within a developing organism. One critical axon guidance molecule is UNC-6/Netrin which bifunctionally directs axon growth toward (i.e. attraction) or away (i.e. repulsion) from the UNC-6. While genetic experiments implicate many molecules in regulating UNC-6 attractive and repulsive signaling, detailed cell biological mechanisms of UNC-6-mediatd axon growth in an intact nervous system remain scarce. The work in this dissertation aims to address this gap by examining the cell and molecular bases of UNC-6 attraction and repulsion. Using cutting-edge time-lapse imaging in living C. elegansnervous systems, I first identify roles for both haptotactic and chemotactic growth during axon attraction. Visualizing the interaction between the growing axon tip and UNC-6 indicates the UNC-40/DCC receptor enriches UNC-6 at the leading edge to stimulate continuous growth. Second, I utilize structural insights from UNC-6 in complex with the UNC-5 receptor to test in vivoroles for heparin sulfate proteoglycans (HSPGs) in axon repulsion in C. elegans. Targeted genetic perturbations indicate that HSPGs amplify the repulsive signaling by UNC-6 and UNC-5. Together, these data provide a common foundation of cell biological principles that drive UNC-6 function through polarization of the growth cone and actin-driven protrusion at the leading edge. .
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https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31901317
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