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Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.

The Journal of comparative neurology | 2009

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior.

Pubmed ID: 19226509 RIS Download

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Antibodies used in this publication

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R56 MH067842
  • Agency: NIMH NIH HHS, United States
    Id: F30 MH083474
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD015052
  • Agency: NIMH NIH HHS, United States
    Id: MH67842
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH067842-05
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH067842
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD015052-27
  • Agency: NIMH NIH HHS, United States
    Id: MH083474
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD15052

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This is a list of tools and resources that we have found mentioned in this publication.


AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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Met (B-2) (antibody)

RRID:AB_673755

This monoclonal targets Met

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