Spatial Transcriptomics reveals brain regional gene expression profiles in murine model of Periventricular Heterotopia
Periventricular Heterotopia (PH) is a malformation of cerebral cortical development characterized by the presence of neurons along the wall of lateral ventricles. The most notable neurological symptoms are seizures that usually first appear when PH becomes evident during the teenage years. Heterozygous loss of function mutations within the FLNA gene in Xq28 are the most frequent cause of familial PH, while the genotype-phenotype correlation has not been well established. We generated a mouse model of PH by conditionally deleting Flna in neural progenitors along with a Flnb null mutation. In this mouse model, periventricular neurons are predominantly generated in postnatal ages. To understand the pathogenesis of PH and the mechanism of postnatal- adult neurogenesis, we assessed transcriptomic alterations resulting from Flna and Flnb double loss of function in the ventricular/subventricular zone (V-SVZ), upper cortical layers, and periventricular neurons, respectively. This dataset reveals spatially-dependent differential gene expressions between PH and their normal control counterparts at 3 months of age. Overall design: Brains of 3 Flna-Flnb double mutant (referred to as FlnKO) and 3 control mice at 3 months of age were fixed by transcardial perfusion with nuclease-free PBS and 4% paraformaldehyde. From the fixed brains cryosections of 7-µm thickness were placed on a microscope slide. The slide was analyzed by GeoMx Digital Spatial Profiler to assess whole transcriptome profiles in selected regions of interests (ROIs) that were identified by staining with fluorescent-conjugated antibodies to NeuN and Gfap.