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The Role of UNC-129 in Axon Guidance...

Beckett Sward, Emily Michele.

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The Role of UNC-129 in Axon Guidance and Cell Migration During Caenorhabditis elegans Development.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of UNC-129 in Axon Guidance and Cell Migration During Caenorhabditis elegans Development./
作者:	Beckett Sward, Emily Michele.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	142 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Contained By:	Dissertations Abstracts International81-06B.
標題:	Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22620522
ISBN:	9781392589946

The Role of UNC-129 in Axon Guidance and Cell Migration During Caenorhabditis elegans Development.
Beckett Sward, Emily Michele.

The Role of UNC-129 in Axon Guidance and Cell Migration During Caenorhabditis elegans Development. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 142 p.

Source: Dissertations Abstracts International, Volume: 81-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

The UNC-6/netrin pathway plays an important role in cell migration and axon guidance. Ventral sources of UNC-6 guide axons from the ventral to dorsal surface by activating the repulsive UNC-5 receptor and UNC-40 co-receptor, and from dorsal to ventral by activating the attractive UNC-40 receptor. In C. elegans, UNC-129 is a TGF-beta family member expressed in dorsal body wall muscles and is thought to promote the interaction between UNC-5 and UNC-40 for long range repulsion away from ventral sources of UNC-6, while inhibiting UNC-5-alone function. The promotion of UNC-5+UNC-40 signaling could act to increase sensitivity where the UNC-6/netrin concentration is relatively low away from its source. unc-130 encodes a transcription factor that represses expression of unc-129 ventrally. In an unc-130(ev505) mutant, UNC-129 is ectopically expressed, effectively abolishing the gradient of UNC-129 causing migration and axon guidance defects. This project aims to provide better understanding of the UNC-129 pathway by 1) investigating potential UNC-129 receptors and 2) characterizing suppressors of ectopic UNC-129 function.PUR-7 is a candidate UNC-129 receptor discovered in silico that shares similarity to the extracellular domain of canonical TGF-beta receptors. A deletion of genomic DNA that deletes pur-7 and part of the neighbouring srd-4 gene enhances the distal tip cell migration and axon guidance defects of a hypomorphic unc-5 allele, and enhances the migration defects of the unc-130 mutant. Efforts to disentangle the genetic interaction of pur-7 from srd-4 were unfortunately not fruitful. The sup7-2 mutant suppresses distal tip cell migration defects in the unc-130(ev505) mutant, suggesting a role in the UNC-129 pathway. Using mapping and bioinformatical analysis, sup7-2 was located to a genomic region between 5-6 Mb on chromosome X. There are mutations in five candidate genes in this region: ifa-4, tbc-7, gakh-1, actl-1 and C03B1.1. RNAi knockdown of gakh-1 and tbc-7 have an effect on unc-130(ev505) DTC migration defects. Injection of fosmids containing tbc-7 rescue the suppression by sup7-2. Although tbc-7 is likely the sup-7-2 gene, both candidates have an effect on DTC migration and are of interest for future study.

ISBN: 9781392589946Subjects--Topical Terms:

530508
Genetics.
Subjects--Index Terms:

Axon guidance

The Role of UNC-129 in Axon Guidance and Cell Migration During Caenorhabditis elegans Development.
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300 $a 142 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
500 $a Advisor: Culotti, Joseph.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2019.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be sold to any third party vendors.
520 $a The UNC-6/netrin pathway plays an important role in cell migration and axon guidance. Ventral sources of UNC-6 guide axons from the ventral to dorsal surface by activating the repulsive UNC-5 receptor and UNC-40 co-receptor, and from dorsal to ventral by activating the attractive UNC-40 receptor. In C. elegans, UNC-129 is a TGF-beta family member expressed in dorsal body wall muscles and is thought to promote the interaction between UNC-5 and UNC-40 for long range repulsion away from ventral sources of UNC-6, while inhibiting UNC-5-alone function. The promotion of UNC-5+UNC-40 signaling could act to increase sensitivity where the UNC-6/netrin concentration is relatively low away from its source. unc-130 encodes a transcription factor that represses expression of unc-129 ventrally. In an unc-130(ev505) mutant, UNC-129 is ectopically expressed, effectively abolishing the gradient of UNC-129 causing migration and axon guidance defects. This project aims to provide better understanding of the UNC-129 pathway by 1) investigating potential UNC-129 receptors and 2) characterizing suppressors of ectopic UNC-129 function.PUR-7 is a candidate UNC-129 receptor discovered in silico that shares similarity to the extracellular domain of canonical TGF-beta receptors. A deletion of genomic DNA that deletes pur-7 and part of the neighbouring srd-4 gene enhances the distal tip cell migration and axon guidance defects of a hypomorphic unc-5 allele, and enhances the migration defects of the unc-130 mutant. Efforts to disentangle the genetic interaction of pur-7 from srd-4 were unfortunately not fruitful. The sup7-2 mutant suppresses distal tip cell migration defects in the unc-130(ev505) mutant, suggesting a role in the UNC-129 pathway. Using mapping and bioinformatical analysis, sup7-2 was located to a genomic region between 5-6 Mb on chromosome X. There are mutations in five candidate genes in this region: ifa-4, tbc-7, gakh-1, actl-1 and C03B1.1. RNAi knockdown of gakh-1 and tbc-7 have an effect on unc-130(ev505) DTC migration defects. Injection of fosmids containing tbc-7 rescue the suppression by sup7-2. Although tbc-7 is likely the sup-7-2 gene, both candidates have an effect on DTC migration and are of interest for future study.
590 $a School code: 0779.
650 4 $a Genetics. $3 530508
650 4 $a Developmental biology. $3 592588
650 4 $a Molecular biology. $3 517296
653 $a Axon guidance
653 $a C. elegans
653 $a Cell migration
653 $a Netrin guidance
653 $a UNC-129
653 $a UNC-130
690 $a 0369
690 $a 0758
690 $a 0307
710 2 $a University of Toronto (Canada). $b Molecular and Medical Genetics. $3 3177543
773 0 $t Dissertations Abstracts International $g 81-06B.
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791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22620522