Hwang, Y.-S. | bioRxiv Science

bioRxiv2025

The Dishevelled C-terminus interacts with the centrosomal protein Kizuna to regulate microtubule organization during ciliogenesis.

Microtubules (MTs) serve as dynamic scaffolds that support diverse cellular processes, including cell division, intracellular transport, and epithelial morphogenesis. In ciliated cells, MTs not only form the axonemal backbone of cilia but also work in tandem with actin to build an apical meshwork that anchors and orients basal bodies. However, the mechanisms regulating apical MT organization during ciliogenesis remain poorly understood. Here, we identify the centrosomal protein Kizuna (Kiz) as a critical regulator of apical MT architecture. Kiz interacts with the C-terminus of Dishevelled 2 (Dvl-C), inducing an open conformation and enabling the recruitment of Protein Kinase C delta (PKC{delta}) to stabilize the apical MT meshwork. This Dvl2-Kiz-PKC{delta} signaling axis is essential for ciliogenesis across multiple contexts, including the formation of primary cilia in the eye, multicilia in the mucociliary epidermis (MCE), and mono-motile cilia in the left-right organizer, the gastrocoel roof plate (GRP). These findings reveal a conserved molecular mechanism linking Dvl2 conformational dynamics to MT organization and highlight Kizuna as a key mediator coupling non-canonical Wnt signaling to ciliogenesis, left-right patterning, and the organization of the apical actin microtubule meshwork in ciliated cells of embryos.

developmental biology↗

bioRxiv2024

Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice.

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean males and female mice, and with multiple reinforcer types.

animal behavior and cognition↗