Background: The liver occupies a central function in homeostasis maintenance. Its functions depend on a fine architecture allowing each parenchymal cell, the hepatocytes, to contact both the vasculature and to contribute to the formation of the bile canaliculi network. To separate two compartment, epithelial cells like hepatocytes must develop a specific organization: polarity. In the liver, the bile canaliculi network and vasculature are organized as two tightly
intertwined networks. To achieve contact with both, the hepatocytes must acquire a complex polarity composed of multiple axes. The study of this organization is the focus of intense research. A lot of attention is put on the understanding of the established structure in the adult organ and the regeneration of this structure in case of injury. With a progressing understanding of this organization comes the interrogation on how it is established during development. Furthermore, a proper understanding of the establishment process is central to develop reliable in vitro systems or organ-on-a-chip approaches. Questions: In this context we have decided to address the following questions:
- When and how is multipolar polarity established. - Can this establishment be correlated to any extracellular cue in vivo. Methods: To address these questions we have fixed, stained, imaged, and reconstructed large volumes of embryonic liver tissue at several consecutive stages of development. We looked at polarized trafficking and junctional markers to follow polarity establishment. We looked at ECM and cell division markers to correlate cues susceptible to guide polarization. We also performed in vitro experiments to further explore the hypotheses formulated along the way based on in vivo observations. Conclusion: This study led us to conclude that multipolar polarity arises from both lumen tubular elongation and multiple lumen formation. The formation of multiple lumina involves the movement of a Rab11 vesicular cluster and independent junctional plate formation. Our study suggests that ZO-1 could be involved in the synchronization between vesicular cluster movement and junction plate formation. Finally, we could not link cell division to polarization, however, we could correlate fibronectin distribution to potential early polarization events.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:82764 |
| Date | 22 December 2022 |
| Creators | Delpierre, Julien |
| Contributors | Zerial, Marino, Solimena, Michele, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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