Cell ‐autonomous impact of polysialic acid‐producing enzyme ST8SIA2 on developmental migration and distribution of cortical interneurons

AbstractIn humans, variations in the polysialic acid ‐producing enzyme ST8SIA2 and disturbances in the cortical inhibitory system are associated with neurodevelopmental psychiatric disorderssuch as schizophrenia and autism. In mice, the ST8SIA2‐dependent formation of polysialic acid during embryonic development is crucial for the establishment of interneuron populations of the medial prefrontal cortex (mPFC). However, the spatial pattern and the neurodevelopmental mechanisms of interneuron changes caused by loss of ST8SIA2 functionhave not been fully characterized. Here, we use immunohistochemical analysis to demonstrate that densities of pa rvalbumin‐positive interneurons are not only reduced in the mPFC, but also in the adjacent motor and somatosensory cortices ofSt8sia2‐deficient male mice. These reductions, however, were confined to the rostral parts of the analyzed region. Mice with conditional knockout ofSt8sia2 under the interneuron ‐specificLhx6 promoter, but not mice with a deletion under theEmx1 promoter that targets cortical excitatory neurons and glia, largely recapitulated the area ‐specific changes of parvalbumin‐positive interneurons in the anterior cortex ofSt8sia2‐/‐ mice. Live imaging of interneuron migration in slice cultures of the developing cortex revealed a comparable reduction of directional persistence accompanied by increased branching of leading processes in slice cultures obtained fromSt8sia2‐/‐ embryos or from embryos with in...

Source: Journal of Neurochemistry - October 13, 2019 Category: Neuroscience Authors: Ute E. Schuster, Charlotte Rossdam, Iris R öckle, Miriam Schiff, Herbert Hildebrandt Tags: Original Article Source Type: research