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Togawa, T.

Publications and source records attributed to Togawa, T..

2 recordsLinked to original sources

Genes responsible for the formation of asymmetrical mandibular teeth in the giant mealworm beetle, Zophobas atratus

ABSTRUCTThe mandibles of coleopteran insects are typical examples of external morphological asymmetry in animals. The developmental molecular mechanisms underlying the external morphological asymmetry remain to be elucidated compared to those of the internal asymmetric organ. In the tenebrionid beetle, Zophobas atratus, the inner teeth of adult mandibles are asymmetric, while the pupal mandibles are nearly symmetric. The asymmetric morphogenesis is assumed to be caused by the left-right regulatory differences of inner teeth formation, but even the developmental mechanisms involved in the inner teeth per se remains unknown. In this study, we investigated the morphogenetic process involved in the formation of inner teeth and searched for genes responsible for this process. Morphological observation showed that the inner teeth of adults formed during 0-5 days after pupal molting. Left mandibles possessed the characteristic second inner teeth, whereas the right mandibles exhibited invaginations between apical and second inner teeth. We performed RNAi for candidate genes and successfully identified four genes (paired, alistaless, Lim1, and mlpt) involved in the formation of inner teeth. Among them, mlpt RNAi had a strong effect on the morphology of the right mandibles, suggesting its involvement in the asymmetrical formation of mandibles.

developmental biology↗

In Vivo Delivery of Therapeutic Molecules by Transplantation of Genome-Edited Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of -Galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified -N-acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules.

cell biology↗