Involvement of strawberry notch homologue 1 in neurite outgrowth of cortical neurons.

When the regulation of axonal and dendritic growth is altered, the neuronal network becomes disordered, which may contribute to the development of psychiatric disorders. Some genome analyses have suggested relationships between mutations in strawberry notch homologue 1 (SBNO1) and neurodevelopmental disorders. However, the function of SBNO1 has not yet been reported. Here, SBNO1 expression pattern during the development of the cerebral cortex in mice was examined. SBNO1 was strongly expressed in the cortical plate and its expression was maintained at a low level during the postnatal stage. CRISPR/Cas9-based knockout of Sbno1 in Neuro2A cultured cells showed delayed growth of neurites. A cortical neuron-specific conditional knockout mouse was constructed, which resulted in hypotrophy of axon bundles and dendrites in cortical neurons. Thus, when mutated, SBNO1 is a candidate gene for psychiatric diseases, such as schizophrenia, as suggested by human genome studies.

Dab1 contributes differently to the morphogenesis of the hippocampal subdivisions.

The hippocampal formation (HF) is morphologically and functionally distinguishable into the subdivisions, such as the dentate gyrus (DG), subiculum, and Ammon's horn. The Ammon's horn is further divided into the CA (Cornu Ammonis)1, CA2, and CA3. The Reelin-Dab1 signal is essential for the morphogenesis of the mammalian brain. In the neocortex of Reelin-Dab1 signal mutants the laminar pattern of the neurons is disrupted along the radial axis. Morphological abnormalities in the HF of the Reelin-Dab1 mutants were known, but how these abnormalities appear during development had not been extensively studied. We examined the morphology of the well-developed Dab1 deficient HF by staining with a silver impregnation method in this report, and found that disruption of lamination in the CA1, CA3, and DG was different. Abnormalities observed in the development of Dab1 deficient CA1 were similar to those reported in the neocortical development, while Dab1 deficient CA3 neuronal progenitors radially spreaded beyond presumptive pyramidal layer. The intermediate progenitor cells ectopically located in the Dab1 deficient DG, but neurogenesis was normal in the CA1 and CA3. These observations suggest that the morphogenesis in these HF subdivisions employs different developmental mechanisms involving Dab1 function.

A mammalian dpy-19 homologue is expressed in GABAergic neurons.

Gsh2 homeobox transcription factors play a crucial role in the development of GABAergic neurons. Caenorhabditis elegans's mab-5 gene is homologous to Gsh2; its expression is controlled by dpy-19. This study produced the polyclonal anti-mammalian DPY-19 (MDPY-19) antibody and showed the distribution of anti-MDPY-19 immunopositive cells. In addition, the mammalian dpy-19 (Mdpy-19) 5'-flanking region was analyzed by in vivo transient transfection assays. Mdpy-19 is expressed in ependymal cells in the adult rat brain, embryonic neuroepithelial cells, and cultured neural stem cells. In the adult rat ventricular zone, immunoreactivity with MDPY-19 of the dorsal area is stronger than that of the ventral area. Embryonic neuroepithelial cells and radial glial cells show strong anti-MDPY-19 immunoreactivity. We created the Mdpy-19 green fluorescent protein (GFP) reporter gene. Our results show that Mdpy-19 is expressed in neural stem cells and progenitor cells, especially radial glial cells. Only ependymal cells among differentiated cells express Mdpy-19 gene. However, the possibility exists that the Mdpy-19 gene is able to transcript in GABAergic neurons. It is suggested that a factor existing in mature neurons withdraws the expression of Mdpy-19.