Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis

Luca Tamagnone, Pietro Fazzari, Junia Penachioni, Sara Gianola, Ferdinando Rossi, Britta J. Eickholt, Flavio Maina, Lena Alexopoulou, Antonino Sottile, Paolo Maria Comoglio, Richard A. Flavell

Risultato della ricerca: Contributo in rivistaArticolo in rivista

59 Citazioni (Scopus)

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. Conclusion. 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. © 2007 Fazzari et al; licensee BioMed Central Ltd.
Lingua originaleEnglish
pagine (da-a)1-12
Numero di pagine12
RivistaBMC Developmental Biology
Volume7
DOI
Stato di pubblicazionePubblicato - 2007

Keywords

  • PlexinB1
  • Sema4D, tumour angiogenesis

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