Extremely grateful to be granted a two year post-doctoral fellowship by @embo.org to study the earliest phases of mutant to malignant cell transition during breast cancer initiation using intravital microscopy. Thank to @vanrheenenlab.bsky.social for the immense support! @nkinl.bsky.social

This work would not have been possible without our many collaborators who provided reagents, lines and much needed support! @ruibenedito.bsky.social, M. Jeansson, @brittae.bsky.social, D. Vestweber, K. Gängel, O. Friedrich, J. van Buul, P. Saharinen, R. Smith and M. Majda and many others!

We propose following model: LECs exhibit dynamic overlaps with a spectrum of junctional configurations. Increase in interstitial fluid volume passively shortens overlaps, facilitating lumen expansion. Actin remodelling drives re-extension of overlaps, reinforcing monolayer integrity and strength.

What mechanisms cause the adoption of the unique shape? Lymphatics continuously dilate and constrict, leading to cyclic isotropic stretch. Isotropic stretching of LEC monolayers in vitro reproduced aspects of in vivo phenotypes, including a wavy junctional organization and cell-cell overlaps.

Interestingly, plant epidermal cells have a strikingly similar lobate shape, which provides structural rigidity. We teamed up with plant biologists R. Smith and M. Majda. In silico modeling showed that, similar to plants, the lobate shape of LECs helps prevent lumen collapse in lymphatic capillaries

Actin dynamics is controlled by Rho-GTPases such as CDC42 and are needed to maintain vessel integrity, as LEC-specific deletion led to cytoskeletal disorganization and loss of monolayer integrity

Intravital imaging of actin using a newly generated inducible R26-LSL-Lifeact-GFP line revealed that actin dynamics likely drive the remodeling of LEC lobes and overlaps, while microtubules contibute to core cellular stability.

By performing intravital imaging of the same capillary LECs over several hours to weeks we found extensive remodelling of their cellular protrusions and overlaps. Entire LEC lobes disappeared and appeared during normal tissue homeostasis, showing the dynamic nature of these cells.

The oak-leaf cell shape of capillary LECs has been described centuries ago. However using the R26-iMb line developed by @ruibenedito.bsky.social enabled us to illuminate individual cells and their overlaps. This analysis showed that overlaps shrink in response to increased fluid volume.

Investigation of lymphatic junctional organization using genetic reporters, immunohistochemistry and classical histology approaches revealed not only classical button junctions, but also a broader spectrum of junctional organizations - suggesting dynamic junctional remodeling.

After 5 years my scientific chapter in Uppsala is coming to an end. Two weeks ago I have successfully defended my PhD thesis at the Mäkinenlab. Big thanks to Taija for being a true mentor and to Holger Gerhardt for acting as my opponent and critically assessing my work.