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Research progress

2014-2015: Proposed research project 10

A mechano-chemical coupling mechanism underlying optic cup morphogenesis in embryonic stem cell-derived tissue culture
Leader : Mototsugu Eiraku
Research progress

During past 2 years, we have sought to elucidate a mechano-chemical coupling in self-organized epithelial morphogenesis using the in vitro culture for optic cup formation. We have focused on spontaneous calcium transients during retinal epithelial invagination and found that spontaneous calcium transients were specifically observed in the hinge region. We also noticed that frequency of the calcium transients correlated with local epithelial curvature, suggesting that there is a feedback mechanism in which each cells in the retinal epithelium can sense tissue shape and regulate own cell morphology in response to global deformation (in preparation). In addition, to analyze the effects of apoptotic cell behaviors on 3D multicellular morphogenesis, we modeled cell apoptosis based on the RNR model framework that is 3D vertex simulation model we have suggested. By perturbation analysis and model-based prediction, we proposed a novel model explaining the optic cup morphogenesis with dorso-ventral polarization (in preparation). Furthermore, we develop a hESC culture method to induce choroid plexus, the most dorsomedial portion of the telencephalon. We found that titrating BMP and Wnt exposure allowed the self-organization of medial pallium tissues. Long-term dissociation culture, these dorsomedial telencephalic tissues give rise to Zbtb20(+)/Prox1(+) granule neurons and Zbtb20(+)/KA1(+) pyramidal neurons, both of which were electrically functional with network formation (Nat Commun 2015). Thus, our approach provides a new experimental platform for the analysis of human hippocampal development and hippocampus-related disorders.