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A homeostatic apical microtubule network shortens cells for epithelial folding via a basal polarity shift

Nature Cell Biology volume 20, pages 36–45 (2018)Cite this article

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Abstract

Epithelial folding is typically driven by localized actomyosin contractility. However, it remains unclear how epithelia deform when myosin levels are low and uniform. In the Drosophila gastrula, dorsal fold formation occurs despite a lack of localized myosin changes, while the fold-initiating cells reduce cell height following basal shifts of polarity via an unknown mechanism. We show that cell shortening depends on an apical microtubule network organized by the CAMSAP protein Patronin. Prior to gastrulation, microtubule forces generated by the minus-end motor dynein scaffold the apical cell cortex into a dome-like shape, while the severing enzyme Katanin facilitates network remodelling to ensure tissue-wide cell size homeostasis. During fold initiation, Patronin redistributes following basal polarity shifts in the initiating cells, apparently weakening the scaffolding forces to allow dome descent. The homeostatic network that ensures size/shape homogeneity is thus repurposed for cell shortening, linking epithelial polarity to folding via a microtubule-based mechanical mechanism.

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Fig. 1: Patronin controls the regularity of columnar cell shape.
Fig. 2: Patronin shapes the apical dome.
Fig. 3: Cortical Patronin undergoes redistribution in response to Par-1 downregulation.
Fig. 4: Excessive Patronin stabilizes microtubules and blocks dome descent.
Fig. 5: Katanin counteracts Patronin to allow cell shortening following basal polarity shifts.
Fig. 6: Patronin recruits Katanin to the apical cortex.
Fig. 7: The Patronin-Katanin circuit promotes remodelling of the apical microtubule network to ensure size homeostasis.
Fig. 8: Dynein-dependent forces scaffold the apical dome shape.

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Acknowledgements

We thank the BACPAC Resources Center at the Children’s Hospital Oakland Research Institute, the Developmental Studies Hybridoma Bank, the Bloomington and Kyoto Drosophila Stock Centers, Y. Bellaiche, J. Grofihans, M. Krahn, J. Raff, D. St Johnston, R. Vale, E. Wieschaus and J. Zallen for sharing reagents; S. Kondo for generation and sharing of the patronin-null alleles as gifts; S. Blythe for assistance with the BAC engineering protocols; A. Momen-Roknabadi for engineering the pBabr plasmid from pTiger; T. Nishimura for assistance with qRT-PCR experiments; A. B. Albero and P. Shankar for advice on data analysis; G. Deshpande, S. Hayashi, S. Lemke, T. Shibata, M. Takeichi and S. K. Yoo for comments on the manuscript; members of the Hayashi, Nishimura, Kuranaga and Yoo laboratories for discussions.

The preparation of some of the reagents used in this work was performed in the laboratory of E. Wieschaus. This work was supported by the core funding at RIKEN Center for Developmental Biology and the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Kakenhi) grant (15H04373) to Y.-C.W.

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  1. Laboratory for Epithelial Morphogenesis, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan

    Michiko Takeda, Mustafa M. Sami & Yu-Chiun Wang

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  1. Michiko Takeda
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Contributions

Y.-C.W. conceived the project, M.T. and Y.-C.W. performed experiments and analysed the data, M.M.S. developed software tools for image processing and analysis, Y.-C.W. wrote the manuscript and all authors approved the final version of the manuscript.

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Correspondence to Yu-Chiun Wang.

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Takeda, M., Sami, M.M. & Wang, YC. A homeostatic apical microtubule network shortens cells for epithelial folding via a basal polarity shift. Nat Cell Biol 20, 36–45 (2018). https://doi.org/10.1038/s41556-017-0001-3

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