title: A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis.
abstract: 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.
authors.affiliation: Pharmacology Institute, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Korostylev
authors.forename: Thomas
authors.initials: T
authors.lastname: Worzfeld
authors.forename: Suhua
authors.initials: S
authors.lastname: Deng
authors.forename: Roland H
authors.initials: RH
authors.lastname: Friedel
authors.forename: Jakub M
authors.initials: JM
authors.lastname: Swiercz
authors.forename: Peter
authors.initials: P
authors.lastname: Vodrazka
authors.forename: Viola
authors.initials: V
authors.lastname: Maier
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hirschberg
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Ohoka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Inagaki
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D007150:Immunohistochemistry; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D039961:Semaphorins