| 研究実績の概要 |
Epithelial folding is typically driven by changes in myosin contractility that acts on the cortical actin meshwork. It remains unclear, however, how tissue deformation arises when myosin levels are low and uniform. Cells that initiate the formation of dorsal folds initially shrink the cell apices and subsequently reduce the apical-basal cell height. Prior to cell shape change, these cells display downregulation of Par-1, the MARK family kinase that specifies the basal-lateral membrane, but the mechanism that causes cell shortening is not known. We show that polarity-coupled cell shortening is controlled by a non-centrosomal microtubule network that is anchored at the apical cortex by the CAMSAP minus end binding protein Patronin. Prior to gastrulation, the apical microtubule network appears to scaffold the apical membrane domain, forming spherical dome shapes, via dynein-dependent pushing forces. The microtubule network ensures the homogeneity of apical dome size across the tissue and such size homeostasis requires the microtubule severing enzyme Katanin that counteracts Patronin in a negative feedback circuit. During dorsal fold initiation, Patronin undergoes basal redistribution as Par-1 becomes downregulated, thereby coupling the cortical scaffold to the basal polarity shifts. Such coupling repurposes the homeostatic microtubule network for the shrinkage of cell apices that ultimately leads to shortening of the initiating cells, which can otherwise be blocked by overexpression of Patronin that abolishes its differential redistribution downstream of Par-1 downregulation.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
As mentioned above, our findings link modulation of polarity to epithelial folding via a novel,
microtubule-based mechanical mechanism. A manuscript describing this work has been recently submitted to and reviewed at a peer-review journal. We are now in the process of revising this manuscript with the goal of having it accepted for publication.
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