Evidence of cell-nonautonomous changes in dendrite and dendritic spine morphology in the met-signaling-deficient mouse forebrain

Matthew C. Judson, Kathie L. Eagleson, Lily Wang, Pat Levitt

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Human genetic findings and murine neuroanatomical expression mapping have intersected to implicate Met receptor tyrosine kinase signaling in the development of forebrain circuits controlling social and emotional behaviors that are atypical in autism-spectrum disorders (ASD). To clarify roles for Met signaling during forebrain circuit development in vivo, we generated mutant mice (Emx1Cre/Metfx/fx) with an Emx1-Cre-driven deletion of signaling-competent Met in dorsal pallially derived forebrain neurons. Morphometric analyses of Lucifer yellow-injected pyramidal neurons in postnatal day 40 anterior cingulate cortex (ACC) revealed no statistically significant changes in total dendritic length but a selective reduction in apical arbor length distal to the soma in Emx1Cre/Metfx/fx neurons relative to wild type, consistent with a decrease in the total tissue volume sampled by individual arbors in the cortex. The effects on dendritic structure appear to be circuit-selective, insofar as basal arbor length was increased in Emx1Cre/Metfx/fx layer 2/3 neurons. Spine number was not altered on the Emx1Cre/Metfx/fx pyramidal cell populations studied, but spine head volume was significantly increased (~20%). Cell-nonautonomous, circuit-level influences of Met signaling on dendritic development were confirmed by studies of medium spiny neurons (MSN), which do not express Met but receive Met-expressing corticostriatal afferents during development. Emx1Cre/Metfx/fx MSN exhibited robust increases in total arbor length (~20%). As in the neocortex, average spine head volume was also increased (~12%). These data demonstrate that a developmental loss of presynaptic Met receptor signaling can affect postsynaptic morphogenesis and suggest a mechanism whereby attenuated Met signaling could disrupt both local and long-range connectivity within circuits relevant to ASD.

Original languageEnglish (US)
Pages (from-to)4463-4478
Number of pages16
JournalJournal of Comparative Neurology
Volume518
Issue number21
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Keywords

  • Anterior cingulate cortex
  • Autism-spectrum disorders
  • Emx1/Met
  • Met receptor tyrosine kinase signaling

ASJC Scopus subject areas

  • Neuroscience(all)

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