Uncontrolled oxidative stress impairs bone formation and induces age-related bone loss in humans. The FoxO family is widely accepted to play an important role in protecting diverse cells from reactive oxygen species (ROS). Activation of FoxO1, the main FoxO in bone, stimulates proliferation and differentiation as well as inhibits apoptosis of osteoblast lineage cells. Despite the important role of FoxO1, little is known about how FoxO1 expression in bone is regulated. Meanwhile, several recent studies reported that microRNAs (miRNAs) could play a role in osteoblast differentiation and bone formation by targeting various transcriptional factors. Here, we identified one additional crucial miRNA, miR-182, which regulates osteoblastogenesis by repressing FoxO1 and thereby negatively affecting osteogenesis. Overexpression of miR-182 in osteoblast lineage cells increased cell apoptosis and inhibited osteoblast differentiation, whereas in vivo overexpression of miR-182 in zebrafish impaired bone formation. From in silico analysis and validation experiments, FoxO1 was identified as the target of miR-182, and restoration of FoxO1 expression in miR-182-overexpressing osteoblasts rescued them from the inhibitory effects of miR-182. These results indicate that miR-182 functions as a FoxO1 inhibitor to antagonize osteoblast proliferation and differentiation, with a subsequent negative effect on osteogenesis. To treat bone aging, an antisense approach targeting miR-182 could be of therapeutic value. ß

The insulation of axons in the vertebrate nervous system by myelin is essential for efficient axonal conduction. Myelination disruption and remyelination failure can cause human diseases, such as multiple sclerosis and hereditary myelin diseases. However, despite progress in understanding myelination regulation, many important questions remain unanswered. To investigate the mechanisms underlying myelination in vivo, we generated transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under the control of the mbp promoter. This transgenic fish displayed faithful EGFP expression in oligodendrocytes and Schwann cells in embryonic and adult zebrafish. Interestingly, although myelination progressed continuously in the postembryonic central nervous system, some of the spinal cord regions were filled with unmyelinated axons even in the adult spinal cord, suggesting functional differences between myelinated and unmyelinated axons. Our results suggest that this transgenic zebrafish could be a valuable animal model to study oligodendrocyte differentiation and myelination in vivo. Developmental Dynamics 239:592-597,

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SignificanceEmotion-related responses, such as fear and anxiety, are important behavioral phenomena in most animal species, as well as in humans. However, the underlying mechanisms of fear and anxiety in animals and in humans are still largely unknown, and anxiety disorders continue to represent a large unmet medical need in the human clinic. Animal models may speed up discovery of these mechanisms and may also lead to betterment of human health. Herein, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of sam2. We observed increased anxiety-related responses in both zebrafish and mouse knockout models. Taken together, these results support a crucial and evolutionarily conserved role of sam2 in regulating anxiety-like behavior.

Cephalopods have the most advanced nervous systems and intelligent behavior among all invertebrates. Their brains provide comparative insights for understanding the molecular and functional origins of the human brain. Although brain maps that contain information on the organization of each subregion are necessary for a study on the brain, no whole brain atlas for adult cephalopods has been constructed to date. Here, we obtained sagittal and coronal sections covering the entire brain of adult Octopus minor (Sasaki), which belongs to the genus with the most species in the class Cephalopoda and is commercially available in East Asia throughout the year. Sections were stained using Hematoxylin and Eosin (H&E) to visualize the cellular nuclei and subregions. H&E images of the serial sections were obtained at 30~70-µm intervals for the sagittal plain and at 40~80-µm intervals for the coronal plain. Setting the midline point of the posterior end as the fiducial point, we also established the distance coordinates of each image. We found that the brain had the typical brain structure of the Octopodiformes. A number of subregions were discriminated by a Hematoxylin-positive layer, the thickness and neuronal distribution pattern of which varied markedly depending upon the region. We identified more than 70 sub-regions based on delineations of representative H&E images. This is the first brain atlas, not only for an Octopodiformes species but also among adult cephalopods, and we anticipate that this atlas will provide a valuable resource for comparative neuroscience research.

Notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. Previously, we identified a novel component of the Notch signaling pathway in zebrafish, mind bomb, which encodes an E3 ubiquitin ligase essential for Notch signal activation. Further studies showed that Mind bomb À/À mouse embryos exhibited pan-Notch phenotypes in various tissues, suggesting that Mind bomb function is conserved in mammals. Therefore we sought to understand the various molecular partners of Mind bomb using yeast two-hybrid screening. In this search we identified Sorting nexin 5 (Snx5) as a novel interacting partner of Mind bomb. Furthermore we demonstrated that Snx5 colocalizes with Mind bomb in early endosomal compartments, suggesting that Snx5 is important for Mind bomb trafficking. In addition, we identified zebrafish orthologue of Snx5 and showed that snx5 is predominantly expressed in hematopoietic and endothelial precursor cells in zebrafish. We also found defects in hematopoiesis and blood vessel development in snx5 morpholino-injected embryos. Taken together, we show that Snx5, a novel interacting partner of Mind bomb, may have an essential role for cell fate determination in early development.

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