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Development, homeostasis, and regeneration of epithelial tissues

In systematic expression analyses, we could show that plexins of the B-subfamily are highly expressed in epithelial cells. Based on these findings, we identified a central role of these plexins in kidney organogenesis. Given that developmental programs are often reactivated during regeneration of epithelial organs, we next studied the significance of B-plexins in epithelial repair. We found that Plexin-B2 and its ligands were essential for kidney repair after acute renal failure, and could identify a Plexin-B2-mediated signaling pathway, which controls the orientation of the mitotic spindle and the alignment of epithelial cell divisions relative to the basement membrane. While normal tubular epithelial cells mostly divide parallel to the basement membrane, Plexin-B2-deficient tubular epithelial cells divide perpendicular to the basement membrane into the tubular lumen, thereby leading to tubular obstruction and loss of kidney function.

Based on our data in the kidney, which unravel a semaphorin-plexin signaling pathway as a central cellular communication mechanism in epithelial repair, we are now interested in a potential functional relevance of the semaphorin-plexin system in cell-cell communication of epithelial stem cells.

Selected publications:

Jiang C, Javed A, Kaiser L, Nava MM, Zhao D, Brandt DT, Fernández-Baldovinos J, Zhou L, Höß C, Sawmynaden K, Oleksy A, Matthews D, Weinstein LS, Gröne HJ, Niessen CM, Offermanns S, Wickström SA, Worzfeld T. (2020).
Mechanochemical control of epidermal stem cell divisions by B-plexins.
bioRxiv. doi: https://doi.org/10.1101/2020.04.30.070359.

Xia, J., Swiercz, J.M., Bañón-Rodríguez, I., Matković, I., Federico, G., Sun, T., Franz, T., Brakebusch, C.H., Kumanogoh, A., Friedel, R.H., Martín-Belmonte, F., Gröne, H.J., Offermanns, S., Worzfeld, T. (2015).
Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair.
Developmental Cell 33, 299-313