Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9.

Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitor cells (OPCs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. However, for oligodendrocytes in the cerebellum, the developmental origins and the molecular machinery to control these distinct steps remain unclear. By in vivo fate mapping and immunohistochemical analyses, we obtained evidence that the majority of oligodendrocytes in the cerebellum originate from the Olig2-expressing neuroepithelial domain in the ventral rhombomere 1 (r1), while about 6% of cerebellar oligodendrocytes are produced in the cerebellar ventricular zone. Furthermore, to elucidate the molecular determinants that regulate their development, we analyzed mice in which the transcription factor Sox9 was specifically ablated from the cerebellum, ventral r1 and caudal midbrain by means of the Cre/loxP recombination system. This resulted in a delay in the birth of OPCs and subsequent developmental aberrations in these cells in the Sox9-deficient mice. In addition, we observed altered proliferation of OPCs, resulting in a decrease in oligodendrocyte numbers that accompanied an attenuation of the differentiation and an increased rate of apoptosis. Results from in vitro assays using oligodendrocyte-enriched cultures further supported our observations from in vivo experiments. These data suggest that Sox9 participates in the development of oligodendrocytes in the cerebellum, by regulating the timing of their generation, proliferation, differentiation and survival.

Cytoskeletal regulation by AUTS2 in neuronal migration and neuritogenesis.

Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. Immunohistochemistry and fractionation studies show that AUTS2 localizes not only in nuclei, but also in the cytoplasm, including in the growth cones in the developing brain. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These findings suggest that cytoplasmic AUTS2 acts as a regulator of Rho family GTPases to contribute to brain development and give insight into the pathology of human psychiatric disorders with AUTS2 mutations.

Diurnal infection patterns and impact of Microcystis cyanophages in a Japanese pond.

Viruses play important roles in regulating the abundance, clonal diversity, and composition of their host populations. To assess their impact on the host populations, it is essential to understand the dynamics of virus infections in the natural environment. Cyanophages often carry host-like genes, including photosynthesis genes, which maintain host photosynthesis. This implies a diurnal pattern of cyanophage infection depending on photosynthesis. Here we investigated the infection pattern of Microcystis cyanophage by following the abundances of the Ma-LMM01-type phage tail sheath gene g91 and its transcript in a natural population. The relative g91 mRNA abundance within host cells showed a peak during the daylight hours and was lowest around midnight. The phage g91 DNA copy numbers in host cell fractions, which are predicted to indicate phage replication, increased in the afternoon, followed by an increase in the free-phage fractions. In all fractions, at least 1 of 71 g91 genotypes was observed (in tested host cell, free-phage, and RNA fractions), indicating that the replication cycle of the cyanophage (i.e., injection, transcription, replication, and release of progeny phages) was occurring. Thus, Microcystis cyanophage infection occurs in a diel cycle, which may depend on the light cycle. Additionally, our data show that the abundance of mature cyanophage produced within host cells was 1 to 2 orders of magnitude greater than that of released phages, suggesting that phage production may be higher than previously reported.