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

AI Article Synopsis

  • - The development of neural circuits relies on several coordinated processes like cell growth, movement, and survival, influenced by hepatocyte growth factor (HGF) signaling through the Met receptor.
  • - Research previously linked a MET gene variant to autism spectrum disorder, indicating that the Met signaling pathway may disrupt brain circuits related to social and emotional functions.
  • - Using various scientific techniques, the study mapped the expression of the Met gene in the mouse forebrain, revealing that its activity is highest during critical developmental weeks when brain connections are forming, suggesting its importance in establishing these circuits.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647986PMC
http://dx.doi.org/10.1002/cne.21969DOI Listing

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