Loss of cilia in primary ciliated cells and multiciliated cells

Abstract: Cilia are evolutionary conserved microtubule-based organelles that project from the cell surface and in which microtubules are nucleated from a modified centriole called the basal body. The presence and functions of cilia have to be well controlled to ensure normal development and organismal health. Indeed, cilia are dynamic structures, and depending on the cell type, cell cycle state and extracellular conditions, they can be removed via disassembly or shedding. For example, cilia can be stably present in quiescent primary ciliated cells and be disassembled when cells re-enter the cell cycle. It is widely considered impossible for MCCs to re-enter their cell cycle and to lose their cilia because of their high degree of specialized differentiation. However, loss of MCCs as well as MCCs with reduced ciliation and cilia loss were observed in human pulmonary conditions and in the embryonic Xenopus mucociliary epidermis during metamorphosis. Thus, it remains unresolved how and why MCCs are lost in these conditions and whether MCCs lose their cilia via disassembly.
In the present thesis work, the molecular and cellular mechanisms of MCC loss were addressed, and the conservation across cell types of molecular players implicated in cilia loss was investigated. During Xenopus laevis epidermis remodeling prior to metamorphosis, MCCs are lost via lateral line induced apoptosis and via trans-differentiation into secretory goblet-like cells. Both processes are dependent on Notch signaling, while the cellular outcome is modulated by JAK/STAT and thyroid hormone signaling. Trans-differentiation is executed through the loss of ciliary gene expression such as pcm1 and foxj1, initiation of mucus production and secretion, remodeling and loss of basal bodies, and mechanisms resembling primary cilia disassembly, such as cilia shortening, axonemal microtubule de-acetylation, PCM1 loss and loss of cell cycle block. Furthermore, this thesis work investigated a conserved role for the centrosomal protein CP110 in cilia loss. In primary cilia undergoing cilia disassembly, CP110 accumulates at the ciliary base and within the ciliary compartment. Its dynamic localization depends on known primary cilia disassembly factors AURKA and PLK1. Additionally, CP110 is found at the ciliary tip of Xenopus epidermal MCCs that have short cilia or/and are over-expressing PLK1.In summary, the data presented in this thesis demonstrate that Xenopus epidermal MCCs can be lost via cell death or trans-differentiation into a non-ciliated cell type (goblet-like cells), and argued for a common mechanism of cilia loss across ciliated cell types in vertebrates by suggesting a novel conserved role of CP110 in cilia loss in primary ciliated cells and multiciliated cells

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2023

Klassifikation und Themen

• Schlagwort: Signaltransduktion

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2023
• Urheber: Tasca, Alexia
• Beteiligte Personen und Organisationen: Walentek, Peter ; Walz, Gerd ; Driever, Wolfgang ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie ; Universitätsklinikum Freiburg

Weitere Informationen

• DOI: 10.6094/UNIFR/233739
• URN: urn:nbn:de:bsz:25-freidok-2337397
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 11:04 MESZ