Membrane protrusion networks in tissue morphogenesis and homeostasis

Three-dimensional tissue architecture depends on a series of transient, precisely coordinated cell-cell interactions that drive growth, signalling, and pattern formation. Our recent identification of the Interplanar Amida Network (IPAN) in the Drosophila pupal wing, a dynamic lattice of vertical and lateral membrane protrusions, uncovers a previously unrecognised mechanism that synchronises cell-cycle transitions and interplanar communication during morphogenesis. Building on this foundation, the project will examine whether tunnelling nanotube (TNT)-like structures operate as a conserved mode of communication in both healthy epithelia and in the earliest stages of neoplastic change.

Using advanced in vivo imaging of the pupal wing, together with an ex vivo wing imaginal disc model of apicobasal polarity loss (_scribble_-deficient tissue), the project will address TNT dynamics, quantify organelle and signalling complex trafficking, and assess corresponding transcriptional responses. A central aim is to determine how TNT/IPAN activity integrates BMP signalling with G2-phase progression and proliferation during normal development, and how TNT-mediated exchanges between wild-type and polarity-compromised cells influence epithelial integrity and growth control.

The project will further identify conserved and context-specific molecular regulators that govern TNT formation, stability, and cargo transport. Collectively, these studies will establish mechanistic principles of TNT-dependent communication in three-dimensional epithelia and inform strategies for selectively disrupting pathological TNT activity in cancer, fibrosis, and regenerative medicine.

Key references:

1. Tran, N.V., Montanari, M.P., Gui, J., Lubenets, D., Fischbach, L.L., Antson, H., Huang, Y., Brutus, E., Okada, Y., Ishimoto, Y., Tõnissoo, T. and Shimmi, O. (2024). Programmed disassembly of a microtubule-based membrane protrusion network coordinates 3D epithelial morphogenesis in Drosophila. EMBO J. 43(4): 568-594.

2. Huang, Y., Gui, J., Myllymäki, S.M., Mikkola, M.L. and Shimmi O. (2023). Coordination of tissue homeostasis and growth by the Scribble-α-Catenin-Septate junction complex. iScience. 26(4):106490.

3. Gui, J., Huang, Y., Montanari, M., Toddie-Moore, D., Kikushima, K., Nix, S., Ishimoto, Y. and Shimmi, O. (2019). Coupling between dynamic 3D tissue architecture and BMP morphogen signaling during Drosophila wing morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 116, 4352-4361.

Profile of the supervisor, professor Osamu Shimmi

Webpage of the research group

Contact of the supervisor - osamu.shimmi@ut.ee