Cell lineage and cis-regulation for a unique GABAergic/glycinergic neuron type in the larval nerve cord of the ascidian Ciona intestinalis

The tunicate Ciona intestinalis larva has a simple central nervous system (CNS), consisting of fewer than 400 cells, which is homologous to the vertebrate CNS. Recent studies have revealed neuronal types and networks in the larval CNS of C. intestinalis, yet their cell lineage and the molecular mechanism by which particular types of neurons are specified and differentiate remain poorly understood. Here, we report cell lineage origin and a cis‐regulatory module for the anterior caudal inhibitory neurons (ACINs), a putative component of the central pattern generator regulating swimming locomotion. The vesicular GABA/glycine transporter gene Ci‐VGAT, a specific marker for GABAergic/glycinergic neurons, is expressed in distinct sets of neurons, including ACINs of the tail nerve cord and others in the brain vesicle and motor ganglion. Comparative genomics analysis between C. intestinalis and Ciona savignyi and functional analysis in vivo identified the cis‐regulatory module responsible for Ci‐VGAT expression in ACINs. Our cell lineage analyses inferred that ACINs derive from A11.116 cells, which have been thought to solely give rise to glial ependymal cells of the lateral wall of the nerve cord. The present findings will provide a solid basis for future studies addressing the molecular mechanism underlying specification of ACINs, which play a critical role in controlling larval locomotion.     

Differentiation of Apical Bud Cells in a Newly Developed Apical Bud Transplantation Model Using GFP Transgenic Mice as Donor

Rodent mandibular incisors have a unique anatomical structure that allows teeth to grow throughout the lifetime of the rodent. This report presents a novel transplantation technique for studying the apical bud differentiation of rodent mandibular incisors. Incisal apical end tissue with green fluorescent protein from transgenic mouse was transplanted to wild type mice, and the development of the transplanted cells were immunohistologically observed for 12 weeks after the transplantation. Results indicate that the green fluorescent apical end tissue replaced the original tissue, and cells from the apical bud differentiated and extended toward the incisal edge direction. The immunostaining with podoplanin also showed that the characteristics of the green fluorescent tissue were identical to those of the original. The green fluorescent cells were only found in the labial side of the incisor up to 4 weeks. After 12 weeks, however, they were also found in the lingual side. Here the green fluorescent cementocyte-like cells were only present in the cementum close to the dentin surface. This study suggests that some of the cells that form the cellular cementum come from the apical tissue including the apical bud in rodent incisors.     

Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952

Optimization of novel azetidine compounds, which we had found as colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors, provided JTE-952 as a clinical candidate with high cellular activity (IC₅₀?=?20?nM) and good pharmacokinetics profile. JTE-952 was also effective against a mouse collagen-induced model of arthritis (mouse CIA-model). Additionally, the X-ray co-crystal structure of JTE-952 with CSF-1R protein was shown to be a Type II inhibitor, and the kinase panel assay indicated that JTE-952 had high kinase selectivity.     

Comparative study on ovarian structures in scorpaenids: possible evolutional process of reproductive mode

The reproductive modes of the Scorpaenidae are extremely varied: oviparity, viviparity, and even spawning of internally fertilized eggs or embryos (zygoparity or embryoparity), as in Helicolenus, are known. The ovarian structure of this family is divided into two types by the arrangement of the stroma and the ovarian cavity. One type is the ovary in which the lamella-like stroma develops from the ovarian hilus located on the dorsal side and where the ovarian cavity is located on the ventral side of ovary, classified as “cystovarian type II-1” by Takano (1989). In the other type, the stroma in the ovary develops radially around the blood circulatory system that traverses the center of the ovary, and then the ovarian cavity surrounds all the ovary, classified as “cystovarian type II-3” by Takano (1989). In the present analysis, previous reports about ovarian structure and the relationship to the reproductive mode of scorpaenids were described, and the ovarian structure of eight genera of Scorpaenidae was examined. The ovary of cystovarian type II-1 is seen only in viviparous genera and is not seen in oviparous genera. However, the cystovarian type II-1 is a general structure in other families of Scorpaeniformes, and this structure could be considered a primitive type of ovary rather than that acquired by the process of evolution from oviparity to viviparity. The ovary of cystovarian type II-3 is seen in all six oviparous genera and the one zygoparous genus examined. The ovary of this type is not found in any other family of teleosts, so it could be a structure originally divided in Scorpaenidae. In the genera having the cystovarian type II-3 ovary, there is a common feature of spawning: a floating egg mass encompassed by the gelatinous material. We postulate that the evolution of reproductive mode in the scorpaenid fishes is as follows: Sebastes and Sebastiscus have a primitive ovary in which viviparity has developed, whereas the genera that spawn a floating egg mass evolved the ovarian structure from primitive type to cystovarian type II-3, and further zygoparity, such as in Helicolenus, evolved from them.