2015 Fiscal Year Annual Research Report
Elucidating the mechanisms underlying epithelial cell height change mediated by modifications of apical-basal polarity
| Project/Area Number |
15H04373
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
WANG YUCHIUN 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (80725995)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Keywords | Epithelial cell height / apical-basal polarity / CAMSAP/Patronin / microtubule homeostasis |
|---|
| Outline of Annual Research Achievements |
In the past year, we had examined the localisation, regulation and function of Patronin, the Drosophila homolog of the CAMSAP family microtubule minus end protector during the initiation of dorsal folds in the early Drosophila embryo. Our data indicate that Patronin becomes associated with the apical cortex under the control of the apical-basal polarity pathway to stabilise a ring-like microtubule structure that is situated underneath the apical dome of the early epithelial cells. During dorsal fold initiation, Patronin localisation expands basally in response to the downregulation of the basal determinant Par-1, followed by shrinkage of the apical dome that leads to cell shortening. We hypothesised that the ring-like apical microtubule network could be maintained in a state of homeostasis as it persists during apical dome shrinkage and cell shortening. In support of this hypothesis, we found that the microtubule severing protein Katanin counteracts Patronin in that its overexpression phenocopies the loss-of-function phenotypes of Patronin, whereas overexpression of Patronin blocks appear to super-stabilises the apical microtubule, thus blocking cell shortening. These data support a model whereby, in the initiating cells, the basal polarity shifts temporarily expand the Patronin protected apical microtubules, whose size is subsequently trimmed by Katanin that is recruited by Patronin itself. Additional experiments will be required to further examine and refine this model.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Our current data support a model whereby the CAMSAP family microtubule minus-end protector Patronin transmits apical-basal polarization signal to control the shape of epithelial apical dome. In the initiating cells, the basal polarity shifts temporarily expand the Patronin protected apical microtubules, whose size is subsequently trimmed by Katanin that is recruited by Patronin itself. We propose that the intrinsic homeostatic nature of the apical microtubule network maintains a constant size of the apical dome. Coupled with shifts in polarity in the initiating cells, these two processes likely underlie the shortening of initiating cells. During dorsal fold formation, changes in epithelial cell height via the homeostatic apical dome that is coupled to apical-basal polarity likely represent a critical step that removes the physical obstruction and create a cleft at the tissue surface such that the neighboring cells could bend over to allow the tissue to fold. More broadly, a polarity-coupled cytoskeletal scaffold that is linked to the cell cortex may represent a general mechanism whereby epithelial cell height is controlled by modification of apical-basal polarity. We think that our data significantly advance our understanding of this novel mode of epithelial folding. Thus, we will soon seek to begin preparation of a manuscript that describes these data.
|
| Strategy for Future Research Activity |
There remain a few issues that need to be addressed prior to preparation of the manuscript. These include the loss-of-function phenotype of Katanin, more detailed analysis of the dynamics of apical microtubule in the wild-type and mutant embryos, and the regulation of Katanin localization. Additional experiments that go beyond the current manuscript will include 1) a structure-function analysis for Patronin that attempts to identify functional domains that define the various loss-of-function phenotypes of Patronin, and 2) exploration of mechanistic, molecular and mechanical links between the apical microtubule ring and the apical dome cortex. These experiments will allow us to better understand 1) how Patronin exerts its various function, in particular its function in controlling the cell shape; 2) how the apical microtubules are connected to the apical cortex. Furthermore, we will explore ontogenetic approaches for locally manipulating the activity of Patronin.
|
Research Products
(1 results)
