title: Focal adhesion dynamics are altered in schizophrenia.
abstract: BACKGROUND
  Evidence from genetic association studies implicate genes involved in neural migration associated with schizophrenia risk. Neural stem/progenitor cell cultures (neurosphere-derived cells) from olfactory mucosa of schizophrenia patients have significantly dysregulated expression of genes in focal adhesion kinase (FAK) signaling, a key pathway regulating cell adhesion and migration. The aim of this study was to investigate whether olfactory neurosphere-derived cells from schizophrenia patients have altered cell adhesion, cell motility, and focal adhesion dynamics.
  
  
  METHODS
  Olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects were used. Cells were assayed for cell adhesion and cell motility and analyzed for integrins and FAK proteins. Focal adhesions were counted and measured in fixed cells, and time-lapse imaging was used to assess cell motility and focal adhesion dynamics.
  
  
  RESULTS
  Patient-derived cells were less adhesive and more motile than cells derived from healthy control subjects, and their motility was reduced to control cell levels by integrin-blocking antibodies and by inhibition of FAK. Vinculin-stained focal adhesion complexes were significantly smaller and fewer in patient cells. Time-lapse imaging of cells expressing FAK tagged with green fluorescent protein revealed that the disassembly of focal adhesions was significantly faster in patient cells.
  
  
  CONCLUSIONS
  The evidence for altered motility and focal adhesion dynamics in patient-derived cells is consistent with dysregulated gene expression in the FAK signaling pathway in these cells. Alterations in cell adhesion dynamics and cell motility could bias the trajectory of brain development in schizophrenia.
authors.affiliation: National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Fan
authors.forename: Greger
authors.initials: G
authors.lastname: Abrahamsen
authors.forename: Richard
authors.initials: R
authors.lastname: Mills
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Calderón
authors.forename: Jing Yang
authors.initials: JY
authors.lastname: Tee
authors.forename: Lisette
authors.initials: L
authors.lastname: Leyton
authors.forename: Wayne
authors.initials: W
authors.lastname: Murrell
authors.forename: Justin
authors.initials: J
authors.lastname: Cooper-White
authors.forename: John J
authors.initials: JJ
authors.lastname: McGrath
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology; D022001:Focal Adhesions / Q000201:enzymology / Q000648:ultrastructure*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000201:enzymology / Q000502:physiology*; D009831:Olfactory Mucosa / Q000166:cytology / Q000502:physiology; D012559:Schizophrenia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Cell migration; disease model; neurodevelopment; patient-derived; schizophrenia; stem cell