{"id":{"repo_id":"columbia-diss","oai_identifier":"oai:academiccommons.columbia.edu:10.7916/D8736Z94"},"canonical_url":"https://search.dev.ndltd.org/etd/columbia-diss/oai:academiccommons.columbia.edu:10.7916/D8736Z94","repository":{"repo_id":"columbia-diss","name":"Columbia University","base_url":"https://academiccommons.columbia.edu/oai"},"display":{"title":"Genetic analysis of novel regulators of neuronal migration in Caenorhabditis elegans: the insulin/IGF-1 signaling pathway, a chromatin-binding factor ZFP-1 (AF10) and endogenous RNAi","abstract":"The generation of functional neural circuitries requires neuronal migration, a central component of proper nervous system development. When defective, it can lead to devastating conditions including epilepsy and mental retardation. In the nematode C. elegans, neurons undergo both short- and long-range migrations that are regulated by conserved pathways. In my thesis study, I explore novel roles for both the insulin/IGF-1 signaling pathway and RNAi factors in neuronal migration by using the embryonic anterior migrations of the hermaphrodite-specific neurons (HSNs) of C. elegans as a model. I demonstrate that the insulin/IGF-1 signaling pathway modulates the activity of the conserved DAF-16/FOXO transcription factor non-autonomously in the hypodermis to regulate HSN migration. Furthermore, I identify PAK-1, a p21-activated kinase, as a downstream target of DAF-16 in the hypodermis. This study is the first to demonstrate a non-autonomous role for both FOXO and Pak1 in neuronal migration. I also implicate a conserved PHD zinc finger protein ZFP-1/AF10 and endogenous RNAi in the regulation of HSN migration. I determine that ZFP-1 affects HSN migration in part through its negative effect on the transcription of the conserved insulin/IGF-1 signaling kinase gene pdk-1 and the modulation of downstream DAF-16 activity. This study expands the limited understanding of the normal developmental roles of both ZFP-1/AF10 and RNAi. Combined, this thesis highlights a requirement for the coordinated activities of DAF-16/FOXO, ZFP-1/AF10 and endogenous RNAi in the establishment of proper neuronal positioning during development.","abstract_html":"The generation of functional neural circuitries requires neuronal migration, a central component of proper nervous system development. When defective, it can lead to devastating conditions including epilepsy and mental retardation. In the nematode C. elegans, neurons undergo both short- and long-range migrations that are regulated by conserved pathways. In my thesis study, I explore novel roles for both the insulin/IGF-1 signaling pathway and RNAi factors in neuronal migration by using the embryonic anterior migrations of the hermaphrodite-specific neurons (HSNs) of C. elegans as a model. I demonstrate that the insulin/IGF-1 signaling pathway modulates the activity of the conserved DAF-16/FOXO transcription factor non-autonomously in the hypodermis to regulate HSN migration. Furthermore, I identify PAK-1, a p21-activated kinase, as a downstream target of DAF-16 in the hypodermis. This study is the first to demonstrate a non-autonomous role for both FOXO and Pak1 in neuronal migration. I also implicate a conserved PHD zinc finger protein ZFP-1/AF10 and endogenous RNAi in the regulation of HSN migration. I determine that ZFP-1 affects HSN migration in part through its negative effect on the transcription of the conserved insulin/IGF-1 signaling kinase gene pdk-1 and the modulation of downstream DAF-16 activity. This study expands the limited understanding of the normal developmental roles of both ZFP-1/AF10 and RNAi. Combined, this thesis highlights a requirement for the coordinated activities of DAF-16/FOXO, ZFP-1/AF10 and endogenous RNAi in the establishment of proper neuronal positioning during development.","abstract_has_math":false,"creators":["Kennedy, Lisa Michelle"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-24T01:44:34Z","subjects":["Genetics","Developmental biology"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.7916/D8736Z94","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Kennedy, Lisa Michelle"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013"]},{"key":"dc:type","label":"Dc Type","values":["Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Genetics","Developmental biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.7916/D8736Z94"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The generation of functional neural circuitries requires neuronal migration, a central component of proper nervous system development. When defective, it can lead to devastating conditions including epilepsy and mental retardation. In the nematode C. elegans, neurons undergo both short- and long-range migrations that are regulated by conserved pathways. In my thesis study, I explore novel roles for both the insulin/IGF-1 signaling pathway and RNAi factors in neuronal migration by using the embryonic anterior migrations of the hermaphrodite-specific neurons (HSNs) of C. elegans as a model. I demonstrate that the insulin/IGF-1 signaling pathway modulates the activity of the conserved DAF-16/FOXO transcription factor non-autonomously in the hypodermis to regulate HSN migration. Furthermore, I identify PAK-1, a p21-activated kinase, as a downstream target of DAF-16 in the hypodermis. This study is the first to demonstrate a non-autonomous role for both FOXO and Pak1 in neuronal migration. I also implicate a conserved PHD zinc finger protein ZFP-1/AF10 and endogenous RNAi in the regulation of HSN migration. I determine that ZFP-1 affects HSN migration in part through its negative effect on the transcription of the conserved insulin/IGF-1 signaling kinase gene pdk-1 and the modulation of downstream DAF-16 activity. This study expands the limited understanding of the normal developmental roles of both ZFP-1/AF10 and RNAi. Combined, this thesis highlights a requirement for the coordinated activities of DAF-16/FOXO, ZFP-1/AF10 and endogenous RNAi in the establishment of proper neuronal positioning during development."]},{"key":"dc:title","label":"Title","values":["Genetic analysis of novel regulators of neuronal migration in Caenorhabditis elegans: the insulin/IGF-1 signaling pathway, a chromatin-binding factor ZFP-1 (AF10) and endogenous RNAi"]}]}],"canonical_facts":{"dc:creator":["Kennedy, Lisa Michelle"],"dc:date":["2013"],"dc:description":["The generation of functional neural circuitries requires neuronal migration, a central component of proper nervous system development. When defective, it can lead to devastating conditions including epilepsy and mental retardation. In the nematode C. elegans, neurons undergo both short- and long-range migrations that are regulated by conserved pathways. In my thesis study, I explore novel roles for both the insulin/IGF-1 signaling pathway and RNAi factors in neuronal migration by using the embryonic anterior migrations of the hermaphrodite-specific neurons (HSNs) of C. elegans as a model. I demonstrate that the insulin/IGF-1 signaling pathway modulates the activity of the conserved DAF-16/FOXO transcription factor non-autonomously in the hypodermis to regulate HSN migration. Furthermore, I identify PAK-1, a p21-activated kinase, as a downstream target of DAF-16 in the hypodermis. This study is the first to demonstrate a non-autonomous role for both FOXO and Pak1 in neuronal migration. I also implicate a conserved PHD zinc finger protein ZFP-1/AF10 and endogenous RNAi in the regulation of HSN migration. I determine that ZFP-1 affects HSN migration in part through its negative effect on the transcription of the conserved insulin/IGF-1 signaling kinase gene pdk-1 and the modulation of downstream DAF-16 activity. This study expands the limited understanding of the normal developmental roles of both ZFP-1/AF10 and RNAi. Combined, this thesis highlights a requirement for the coordinated activities of DAF-16/FOXO, ZFP-1/AF10 and endogenous RNAi in the establishment of proper neuronal positioning during development."],"dc:identifier":["https://doi.org/10.7916/D8736Z94"],"dc:language":["English"],"dc:subject":["Genetics","Developmental biology"],"dc:title":["Genetic analysis of novel regulators of neuronal migration in Caenorhabditis elegans: the insulin/IGF-1 signaling pathway, a chromatin-binding factor ZFP-1 (AF10) and endogenous RNAi"],"dc:type":["Theses"]},"updated_at":"2026-07-24T01:44:34Z"}