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Evidence of cell‐nonautonomous changes in dendrite and dendritic spine morphology in the met‐signaling–deficient mouse forebrain
Author(s) -
Judson Matthew C.,
Eagleson Kathie L.,
Wang Lily,
Levitt Pat
Publication year - 2010
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22467
Subject(s) - biology , dendrite (mathematics) , dendritic spine , forebrain , morphology (biology) , spine (molecular biology) , neuroscience , anatomy , microbiology and biotechnology , central nervous system , genetics , hippocampal formation , geometry , mathematics
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 (Emx1 Cre /Met fx/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 Emx1 Cre /Met fx/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 Emx1 Cre /Met fx/fx layer 2/3 neurons. Spine number was not altered on the Emx1 Cre /Met fx/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. Emx1 Cre /Met fx/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. J. Comp. Neurol. 518:4463–4478, 2010. © 2010 Wiley‐Liss, Inc.