title: Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis.
abstract: BACKGROUND
  Semaphorin 3A (Sema3A) is a neural guidance cue that also mediates cell migration, proliferation and apoptosis, and inhibits branching morphogenesis. Because we have shown that genetic deletion of neuropilin-1, which encodes an obligatory Sema3A co-receptor, influences airspace remodeling in the smoke-exposed adult lung, we sought to determine whether genetic deletion of Sema3A altered distal lung structure.
  
  
  METHODS
  To determine whether loss of Sema3A signaling influenced distal lung morphology, we compared pulmonary histology, distal epithelial cell morphology and maturation, and the balance between lung cell proliferation and death, in lungs from mice with a targeted genetic deletion of Sema3A (Sema3A(-/-)) and wild-type (Sema3A(+/+)) littermate controls.
  
  
  RESULTS
  Genetic deletion of Sema3A resulted in significant perinatal lethality. At E17.5, lungs from Sema3A(-/-) mice had thickened septae and reduced airspace size. Distal lung epithelial cells had increased intracellular glycogen pools and small multivesicular and lamellar bodies with atypical ultrastructure, as well as reduced expression of type I alveolar epithelial cell markers. Alveolarization was markedly attenuated in lungs from the rare Sema3A(-/-) mice that survived the immediate perinatal period. Furthermore, Sema3A deletion was linked with enhanced postnatal alveolar septal cell death.
  
  
  CONCLUSIONS
  These data suggest that Sema3A modulates distal pulmonary epithelial cell development and alveolar septation. Defining how Sema3A influences structural plasticity of the developing lung is a critical first step for determining if this pathway can be exploited to develop innovative strategies for repair after acute or chronic lung injury.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Patrice.Becker@questcor.com
authors.forename: Patrice M
authors.initials: PM
authors.lastname: Becker
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Tran
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Delannoy
authors.forename: Chaoxia
authors.initials: C
authors.lastname: He
authors.forename: John M
authors.initials: JM
authors.lastname: Shannon
authors.forename: Sharon
authors.initials: S
authors.lastname: McGrath-Morrow
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D038081:Organogenesis / Q000235:genetics / Q000502:physiology*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*
chemical_list: D040121:Semaphorin-3A
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