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Function of the mechano-gated ion channel NompC in tissue morphogenesis
Mechanosensitive ion channels have long been investigated in the field of neurobiology. However, their roles in other tissues, especially in epithelial tissues, remained elusive. Epithelial cells, being closely packed in tissues, can sense and are able to respond to the mechanical forces generate...
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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2023
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| Zusammenfassung: | Mechanosensitive ion channels have long been investigated in the field of
neurobiology. However, their roles in other tissues, especially in epithelial tissues,
remained elusive. Epithelial cells, being closely packed in tissues, can sense and are
able to respond to the mechanical forces generated and transmitted by their neighbours.
Such mechanical communication among epithelial cells is classically achieved via the
cadherin-catenin complexes at the cell junctions. The mechanical signals received by
the mechanomolecules are thereafter either directly transmitted through the cytoskeletal
reorganisation or are transduced into biochemical signals inside the cells. We
hypothesised that mechanosensitive ion channels can also act as mechanomolecules in
epithelial cells.
Based on the previous findings, I went on to investigate if NompC, the first to
be known mechanosensitive channel in Drosophila, is expressed in the epithelial cells
too and, if so, what purpose it serves there. I have found a widespread expression of the
NompC channel in multiple tissues, including the amnioserosa, a highly dynamic and
short-lived epithelial tissue during dorsal closure, a major morphogenetic
transformation event in Drosophila. The absence of NompC led to multiple defects in
the dorsal closure process. Amnioserosa cells exhibit a high degree of coordination,
manifested through a synchronised oscillatory behaviour between neighbouring cells.
My study revealed that NompC is a critical regulator of this synchrony.
I also found that NompC is responsive to mechanical forces in the amnioserosa
tissue and drives Ca2+ influx into the cells. Depletion of NompC caused a disruption in
directional force distribution across the tissue and an anisotropic cellular morphology.
I found NompC is important to facilitate active cell oscillation. An absence of NompC
disables the cells to relay external mechanical inputs across the tissue efficiently. I
found several interesting cytoskeletal changes that directly or indirectly are supposed
to be affected by NompC as the molecular basis that translates into the downstream
tissue-scale behaviour. In brief, this study provides us with a clear understanding of the
roles of a mechanosensitive ion channel, NompC, in epithelial cells. However, more
research is needed to elucidate the gating activity and the interacting partners of the
NompC channel. |
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| DOI: | 10.17192/z2023.0661 |