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Objective: We investigated whether neural stem cells (NSC) with transgenic expression of human nerve growth factor (hNGF) transplanted into the brain could offer a therapeutic option for the treatment of Alzheimer’s disease (AD). Methods: We infused okadaic acid into rat lateral ventricles to establish a chronic AD animal model. In addition, NSC were stably transduced with hNGF and enhanced green fluorescent protein (eGFP) genes (NSC-hNGF-eGFP) by using a recombination adeno-associated virus serotype 2 (rAAV2) vector. These genetically modified stem cells were grafted into the cerebral cortex of AD rats. Results: AD model rats showed significant damage in learning and memory function, with the formation of senile plaques and neurofibrillary tangles in the cerebral cortex. The transferred hNGF gene conferred stable and high levels of protein expression in NSC in vitro. Moreover, the NSC-hNGF-eGFP, but not the NSC, survived, integrating into the host brain and enhancing cognitive performance after transplantation. Conclusion: The injection of okadaic acid into rat lateral ventricles constitutes a promising animal model for investigating selective aspects of AD. rAAV2-mediated hNGF delivery can render long-term and stable transduction of hNGF in NSC. NSC-hNGF-eGFP transplantation may offer a viable therapeutic approach for treatment of AD.

In early neural development, active cell proliferation and apoptosis take place concurrent with cell differentiation, but how these processes are coordinated remains unclear. In this study, we characterized the role of XBtg2 in Xenopus neural development. XBtg2 transcripts were detected at the edge of the anterolateral neural plate and the neural crest region at the midneurula stage, and in eyes and in part of the neural tube at the tailbud stage. Translational inhibition of XBtg2 affected anterior neural development and impaired eye formation. XBtg2 depletion altered the expression patterns of the early neural genes, Zic3 and SoxD, at the midneurula stage, but not at the early neurula stage. At the midneurula stage, XBtg2-depleted embryos exhibited a marked decrease in the expression of anterior neural genes, En2, Otx2, and Rx1, withoutany changes in neural crest genes, Slug and Snail, or an epidermal gene, XK81. These results suggest that XBtg2 is required for the differentiation of the anterior neural plate from the midneurula stage, but not for the specification of the fate and patterning of the neural plate. XBtg2-depleted embryos also exhibited an increase in both proliferation and apoptosis in the anterior neural plate; however, the altered expression patterns of neural markers were not reversed by inhibition of either the cell cycle or apoptosis. Based on these data, we propose that XBtg2 plays an essential role in the anterior neural development, by regulating neural cell differentiation, and, independently, cell proliferation and survival.

An understanding of the regulation of kidney development has increased dramatically in the past decade. The pronephros, mesonephros, and metanephros represent three distinct renal organs that function, in succession, as the vertebrate excretory system during development of the kidney. These three organ systems are derived from the intermediate mesoderm and develop in a well-defined temporal and spatial sequence. The pronephros, which consists of a tubule, duct and glomus, is established first and is the simplest of the excretory organs in vertebrates. Xenopus pronephros serves as an ideal model for investigating organogenesis and development of renal function in vertebrates. In this article, we highlight the advantages of Xenopus for analyzing kidney organogenesis and the latest research in pronephros development.

Objective: To induce experimental split cord malformations (SCMs) produced through the surgical induction of a dorsal midline fistula. Methods: In addition, the theory of embryogenesis of SCMs was verified by examining the developmental process of this experimentally induced anomaly. In Cynopus pyrrhogaster (amphibian) embryos (stage 18), the neural plate and notochord were split regionally to construct a fistula that appeared to be the ectopic neurenteric canal. Following this procedure, the embryonic development was traced morphologically and histologically. Results: Following the incubation and breeding period, split cord malformation was observed in some animals. Scoliosis, spina bifida, vertebral anomaly and subcutaneous manifestations were also observed with SCMs. Conclusions: The observations made in these experimentally induced SCMs are consistent with the findings in human SCMs. We report an experimental animal model of split cord malformation, in which double spinal cords were developed in the spinal canal. In addition, we examined the embryogenesis of SCMs. This study indicates that SCMs may arise through a process of dorsal midline fistula of the neural plate.

Activin possesses mesoderm-inducing activity, erythroid-differentiating activity, and follicle-stimulating hormone-releasing activity. The chemical structures of the activin molecule are formed by a combination of two beta-subunit peptides of inhibin. Inhibin is a dimer consisting of an alpha and beta subunit. To examine the mesoderm-inducing activity of these substances, we tested several configurations including: (1) two types of alpha-subunit peptide; (2) two types of inhibin A and B dimer; (3) beta A-subunit peptide monomer; (4) three types of activins A, AB and B, and (5) follistatin (activin-binding protein) by the animal cap assay using Xenopus laevis ectoderm, and by the erythroid-differentiating factor (EDF) test. Activins, which are composed of dimeric inhibin beta A- or beta B-subunit peptides, had the highest mesoderm-inducing and EDF activities. The monomeric beta A-subunit peptide exhibited mesoderm-inducing and EDF activities that were much lower than activin A. The inhibitory effect of follistatin on mesodermal induction by the beta A-subunit peptide was also lower than that of activin. Both inhibins A and B had very weak mesoderm-inducing activity and no EDF activity. The two types of inhibin alpha-subunit monomer had little mesoderm-inducing activity and no EDF activity. The mesoderm induction caused by activin A was not suppressed by the addition of the alpha-subunit monomer and inhibin. The mesoderm-inducing activity in relation to the chemical structures of the monomeric and/or dimeric inhibin alpha and beta A subunits is discussed.