Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, are involved in the development of the forebrain, and MET has been identified as a susceptibility loci for autism. In neural tissue, HGF/SF binding to Met induces a signaling cascade that can influence cell migration, proliferation, and formation of neurite processes. Previous studies have shown that grey and white matter volumes are altered in individuals with ASD relative to healthy controls.
Objectives:
HGF/SF and Met are known to be expressed in the developing telencephalon, and changes in HGF/SF or Met expression appear to alter proliferation and formation of processes in neurons. This study employed mutant mice with a targeted mutation of Met in the cerebral cortex and hippocampus to examine how changes in HGF/SF-Met signaling could lead to structural alterations in the forebrain.
Methods:
We employed a mouse line with a floxed Met allele coupled with an Emx1-Cre driver to ablate Met signaling in the cerebral cortex and hippocampus beginning on embryonic day 10.5. This study used structural MRI imaging as well as histological and immunocytochemical techniques to examine the effects of this mutation on brain structure in adult as well as post-natal day 30 (P30) mice.
Results:
Adult mice lacking normal Met expression in the cerebral cortex show alterations in both white and grey matter structures, including the cortex, corpus callosum, hippocampus, and striatum. Most structures are unaffected in P30 mice. Histological analysis also shows altered cortical lamination in these mice.
Conclusions: Our data suggest that loss of Met function in the cerebral cortex and hippocampus can lead to anatomical changes in both cortical and sub-cortical structures.