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First published online 17 September 2008
doi: 10.1242/dev.019760

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A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis

Alexander Korostylev^1,*, Thomas Worzfeld^1,*, Suhua Deng¹, Roland H. Friedel², Jakub M. Swiercz¹, Peter Vodrazka¹, Viola Maier², Alexandra Hirschberg¹, Yoshiharu Ohoka³, Shinobu Inagaki³, Stefan Offermanns¹ and Rohini Kuner^1,

¹ Pharmacology Institute, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany.
² Institute of Developmental Genetics, Helmholtz Center Munich, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
³ Group of Neurobiology, School of Allied Health Sciences, Osaka University Faculty of Medicine, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan.

Author for correspondence (e-mail: rohini.kuner{at}pharma.uni-heidelberg.de)

Accepted 12 August 2008

Semaphorins and their receptors, plexins, carry out important functions during development and disease. In contrast to the well-characterized plexin A family, however, very little is known about the functional relevance of B-type plexins in organogenesis, particularly outside the nervous system. Here, we demonstrate that plexin B1 and its ligand Sema4d are selectively expressed in epithelial and mesenchymal compartments during key steps in the genesis of some organs. This selective expression suggests a role in epithelial-mesenchymal interactions. Importantly, using the developing metanephros as a model system, we have observed that endogenously expressed and exogenously supplemented Sema4d inhibits branching morphogenesis during early stages of development of the ureteric collecting duct system. Our results further suggest that the RhoA-ROCK pathway, which is activated downstream of plexin B1, mediates these inhibitory morphogenetic effects of Sema4d and suppresses branch-promoting signalling effectors of the plexin B1 signalling complex. Finally, mice that lack plexin B1 show early anomalies in kidney development in vivo. These results identify a novel function for plexin B1 as a negative regulator of branching morphogenesis during kidney development, and suggest that the Sema4d-plexin B1 ligand-receptor pair contributes to epithelial-mesenchymal interactions during organogenesis via modulation of RhoA signalling.

Key words: Kidney development, RhoA, ROCK, Epithelial-mesenchymal interaction, Transgenic mouse

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				J. M. Swiercz, T. Worzfeld, and S. Offermanns Semaphorin 4D Signaling Requires the Recruitment of Phospholipase C{gamma} into the Plexin-B1 Receptor Complex Mol. Cell. Biol., December 1, 2009; 29(23): 6321 - 6334. [Abstract] [Full Text] [PDF]

				A. Korostylev, T. Worzfeld, S. Deng, R. H. Friedel, J. M. Swiercz, P. Vodrazka, V. Maier, A. Hirschberg, Y. Ohoka, S. Inagaki, et al. A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis. J. Cell Sci., October 15, 2008; 121(20): e1 - e1. [Full Text]