Disruption of cerebral cortex MET signaling in autism spectrum disorder

Daniel B. Campbell, Rosanna D'Oronzio, Krassi Garbett, Philip J. Ebert, Karoly Mirnics, Pat Levitt, Antonio M. Persico

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


Objective: Multiple genes contribute to autism spectrum disorder (ASD) susceptibility. One particularly promising candidate is the MET gene, which encodes a receptor tyrosine kinase that mediates hepatocyte growth factor (HGF) signaling in brain circuit formation, immune function, and gastrointestinal repair. The MET promoter variant rs1858830 allele "C" is strongly associated with ASD and results in reduced gene transcription. Here we examined expression levels of MET and members of the MET signaling pathway in postmortem cerebral cortex from ASD cases and healthy control subjects. Methods: Protein, total RNA, and DNA were extracted from postmortem temporal cortex gray matter samples (BA 41/42, 52, or 22) belonging to eight pairs of ASD cases and matched control subjects. MET protein expression was determined by Western blotting; messenger RNA expression of MET and other related transcripts was assayed by microarray and quantitative reverse transcriptase polymerase chain reaction. Results: MET protein levels were significantly decreased in ASD cases compared with control subjects. This was accompanied in ASD brains by increased messenger RNA expression for proteins involved in regulating MET signaling activity. Analyses of coexpression of MET and HGF demonstrated a positive correlation in control subjects that was disrupted in ASD cases. Interpretation: Altered expression of MET and related molecules suggests dysregulation of signaling that may contribute to altered circuit formation and function in ASD. The complement of genes that encode proteins involved in MET activation appears to undergo long-term compensatory changes in expression that may be a hallmark contribution to the pathophysiology of ASD.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalAnnals of Neurology
Issue number3
StatePublished - Sep 2007
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Disruption of cerebral cortex MET signaling in autism spectrum disorder'. Together they form a unique fingerprint.

Cite this