The Role of Septin Filaments in Neural Crest Cell Migration

Files
KHO-PRIMARY-2025.pdf (4.35 MB)
1764901791831-Video A1.MOV (7.55 MB)
1764901796573-Video A2.MOV (3.6 MB)
1764901801773-Video A3.MOV (4.59 MB)
1764901807574-Video A4.MOV (8.49 MB)
Author(s)
Kho, Mary Elizabeth
Advisor(s)
Editor(s)
Associated Organization(s)
Organizational Unit
Organizational Unit
School of Biology
School established in 1959; merged with School of Applied Physiology in 2016 to become the School of Biological Sciences
Series
Series
Collections
Theses and Dissertations
Supplementary to:
Permanent Link

 https://hdl.handle.net/1853/80578
Abstract
Septin filaments are the fourth member of the cytoskeleton, along with actin microfilaments, microtubules, and intermediate filaments. Since their discovery over 50 years ago, septin filaments have been found to play integral roles in different cellular processes. Recent studies in metastatic cancer cell lines have reported that septin filaments promote cell migration, but a mechanism for their regulation of directed cell migration is still unclear. In this thesis, we utilize the highly similar and established cell migration model of neural crest cells to answer this question. This thesis is structured into three related projects that examine the relationship between septin filaments and their interaction partners in coordinating directed cell migration. The first project focuses on the requirement of septin filament assembly in neural crest cells and the interaction of septin filaments with actin and Cdc42ep1 in neural crest cell migration. Specifically, we found that Cdc42ep1 and septin filaments reciprocally regulate each other and that septin filaments regulate the persistent orientation of actin stress fiber formation and contraction necessary for neural crest cell migration. The second project investigates the role of the actin-binding protein myosin II as a mediator for the septin regulation of actin stress fibers. We found that the direct interaction between septins and myosin II is required to support the persistent migration of neural crest cells. The third project focuses on PAR-1 kinase and its regulation of Cdc42ep1 activity in neural crest cells. We found that PAR-1 kinase is required for neural crest cell migration and that PAR-1 phosphorylation regulates the subcellular organization of Cdc42ep1 in a manner reminiscent of the septin regulation of Cdc42ep1. Together, we propose a model in which septin filaments, Cdc42ep1, and actomyosin coordinate in directed and effective migration of neural crest cells. Importantly, this work reveals the fundamental role of septin filaments in coordinating cytoskeletal dynamics for directed cell migration. This activity is likely conserved during metastatic cancer cell migration.
Sponsor
Date
2025-12
Extent
Resource Type
Text
Resource Subtype
Dissertation (PhD)
Rights Statement
Rights URI