title: Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.
abstract: BACKGROUND
  Plexins are a large family of transmembrane receptors for the Semaphorins, known for their role in the assembly of neural circuitry. More recently, Plexins have been implicated in diverse biological functions, including vascular growth, epithelial tissue morphogenesis and tumour development. In particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role in neural development and in tumour angiogenesis, based on in vitro studies. However, the tissue distribution of PlexinB1 has not been extensively studied and the functional relevance of this receptor in vivo still awaits experimental testing. In order to shed light on PlexinB1 function in vivo, we therefore undertook the genomic targeting of the mouse gene to obtain loss of function mutants.
  
  
  RESULTS
  This study shows that PlexinB1 receptor and its putative ligand, Sema4D, have a selective distribution in nervous and epithelial tissues during development and in the adult. PlexinB1 and Sema4D show largely complementary cell distribution in tissues, consistent with the idea that PlexinB1 acts as the receptor for Sema4D in vivo. Interestingly, PlexinB1 is also expressed in certain tissues in the absence of Sema4D, suggesting Sema4D independent activities. High expression of PlexinB1 was found in lung, kidney, liver and cerebellum. Mutant mice lacking expression of semaphorin receptor PlexinB1 are viable and fertile. Although the axon collapsing activity of Sema4D is impaired in PlexinB1 deficient neurons, we could not detect major defects in development, or in adult histology and basic functional parameters of tissues expressing PlexinB1. Moreover, in the absence of PlexinB1 the angiogenic response induced by orthotopically implanted tumours was not affected, suggesting that the expression of this semaphorin receptor in endothelial cells is redundant.
  
  
  CONCLUSIONS
  Our expression analysis suggests a multifaceted role of PlexinB1 during mouse development and tissue homeostasis in the adult. Nonetheless, the genetic deletion of PlexinB1 does not result in major developmental defects or clear functional abnormalities. We infer that PlexinB1 plays a redundant role in mouse development and it is not strictly required for tumour induced angiogenesis.
authors.affiliation: Institute for Cancer Research and Treatment, University of Torino Medical School, Division of Molecular Oncology, Candiolo, Turin, Italy. p.fazzari@yahoo.it <p.fazzari@yahoo.it>
authors.forename: Pietro
authors.initials: P
authors.lastname: Fazzari
authors.forename: Junia
authors.initials: J
authors.lastname: Penachioni
authors.forename: Sara
authors.initials: S
authors.lastname: Gianola
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.forename: Britta J
authors.initials: BJ
authors.lastname: Eickholt
authors.forename: Flavio
authors.initials: F
authors.lastname: Maina
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Antonino
authors.initials: A
authors.lastname: Sottile
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Comoglio
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Luca
authors.initials: L
authors.lastname: Tamagnone
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000254:growth & development; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development; D007150:Immunohistochemistry; D008546:Melanoma, Experimental / Q000098:blood supply; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; C103150:Sema4d protein, mouse; D039961:Semaphorins