Biology subjects

Onoue, K.

Publications and source records attributed to Onoue, K..

2 recordsLinked to original sources

bioRxiv2025

Genome-edited retinal organoids restore host bipolar connectivity in the primate macula

Retinal organoids (ROs) represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but whether host cone bipolar cells (BCs) in the primate macula can rewire with transplanted photoreceptors remains unresolved. Here, we transplanted genome-edited human retinal organoids lacking ON-BCs (Islet-1-/- ROs) into a non-human primate macular degeneration model. Remarkably, host rod and cone BCs extended dendrites toward grafted photoreceptors, forming functional synapses confirmed by immunohistochemistry, ultrastructural imaging, and focal macular electroretinography. Both ON- and OFF-pathway connectivity was rebuilt, providing the first demonstration of host-graft synaptic integration in the primate macula. These results establish that primate cone circuits retain a surprising capacity for rewiring and highlight genome-edited ROs as a powerful platform for vision restoration. Our findings represent a critical translational step toward stem cell-based therapies capable of repairing central vision in patients with advanced macular degeneration.

neuroscience↗

bioRxiv2021

Tracheal motile cilia require CAMSAP3 for formation of central microtubule pair and coordinated beating

Motile cilia of multiciliated epithelial cells undergo synchronized beating to produce fluid flow along the luminal surface of various organs. Each motile cilium consists of an axoneme and a basal body, which are linked by a transition zone. The axoneme exhibits a characteristic 9+2 microtubule arrangement important for ciliary motion, but how this microtubule system is generated is not yet fully understood. Here we show that CAMSAP3, a protein that can stabilize the minus end of a microtubule, concentrates at multiple sites of the cilium-basal body complex, including the upper region of the transition zone or the axonemal basal plate where the central pair of microtubules (CP) initiates. CAMSAP3 dysfunction resulted in loss of the CP and partial distortion of the basal plate, as well as the failure of multicilia to undergo synchronized beating. These findings suggest that CAMSAP3 plays pivotal roles in the formation or stabilization of the CP by localizing at the basal region of the axoneme, and thereby supports the coordinated motion of multicilia in airway epithelial cells.

cell biology↗