Functional characterisation of novel crumbs complex interactors in the context of epithelial morphogenesis
The Crumbs (CRB) complex is critical for the establishment of epithelial polarity and occupies a distinct domain above the tight junction (TJ), the Vertebrate Marginal Zone (VMZ). Many novel VMZ components were identified, but their functions are unclear. Moreover, when and how the VMZ separates...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2024
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| Online Access: | https://hdl.handle.net/10356/181212 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | The Crumbs (CRB) complex is critical for the establishment of epithelial
polarity and occupies a distinct domain above the tight junction (TJ), the
Vertebrate Marginal Zone (VMZ). Many novel VMZ components were
identified, but their functions are unclear. Moreover, when and how the VMZ
separates from TJ is unknown. The goal of this project is to elucidate the
function and spatio-temporal regulation of the VMZ, especially in the context
of epithelial lumen morphogenesis. To address this, I applied a combination of
loss-of-function approaches in 2D and 3D MDCK cell culture models,
biochemical methods, and light and electron microscopy. I demonstrate that the
VMZ separates from TJ during early stages of lumen formation, and that apical
membrane trafficking to the nascent lumen is mediated by Vacuolar Apical
Compartments (VACs). I also show that CRB and its novel interactors are
essential for normal epithelial polarity development and lumen formation. |
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