Biology subjects

Asakawa, M.

Publications and source records attributed to Asakawa, M..

3 recordsLinked to original sources

bioRxiv2026

Reciprocal regulation of Wnt, receptor and Dvl localizations during cell polarization

Migrating cells use multiple mechanisms to interpret signaling gradients and establish polarity. However, how non-migrating cells interpret such gradients remains poorly understood. In C. elegans, the polarity of asymmetrically dividing seam cells is redundantly regulated by three Wnt proteins: CWN-1, CWN-2, and EGL-20. Here, we show that these Wnts, their receptors, and Dishevelled (Dvl) proteins localize asymmetrically to the posterior side of seam cells in an interdependent manner. The receptors and Dvl colocalize in Wnt-dependent, membrane-associated puncta resembling signalosomes. These findings support positive-feedback mechanisms that links Wnt localization to cell polarity. Because posteriorly expressed CWN-1 and EGL-20 have instructive roles in seam cell polarity, this mechanism may help cells interpret their gradients. In contrast, despite its anterior expression, CWN-2 localizes posteriorly, suggesting that intrinsic polarity cues also contribute to Wnt localization. Together, these findings suggest that feedback integrates Wnt gradients with intrinsic polarity cues to robustly orient cell polarity.

developmental biology↗

bioRxiv2025

Differential functions of multiple Wnts and receptors in cell polarity regulation in C. elegans

Metazoan species possess multiple Wnt ligands and receptor genes that regulate diverse developmental processes. Because these genes often act redundantly, analysis of single-gene mutants does not necessarily reveal the full roles of Wnt signaling. In C. elegans, three Wnt genes (cwn-1, egl-20, and cwn-2) and three receptor genes (lin-17/Fzd, mom-5/Fzd, and cam-1/Ror) redundantly regulate the polarity of asymmetrically dividing seam cells. Here, we comprehensively analyzed genetic interactions among these Wnt and receptor genes. In mom-5 mutant backgrounds, additional mutations in Wnt genes disrupted cell polarization. In contrast, in cam-1 mutant backgrounds, Wnt mutations frequently caused abnormal polarity orientation. These findings indicate that MOM-5 and CAM-1 play distinct roles in establishing cell polarization and determining its orientation, respectively. lin-17 mutations suppressed polarity reversal in multiple Wnt compound mutants, suggesting that LIN-17 may function as a molecular switch for polarity orientation. Although all three Wnt genes regulate polarity orientation in a gradient-independent manner in the absence of receptor mutations, in lin-17 mutant backgrounds, reversing the expression gradients of cwn-1 and egl-20, but not cwn-2, enhanced polarity reversal. This suggests that cwn-1 and egl-20 act not only permissively but also instructively to regulate polarity orientation. Together, our results reveal distinct and cooperative functions of multiple Wnt ligands and receptors that ensure robust control of cell polarity.

developmental biology↗

bioRxiv2024

Distinct functions of three Wnt proteins control mirror-symmetric organogenesis in the C. elegans gonad

Organogenesis requires the proper production of diverse cell types and their positioning/migration. However, the coordination of these processes during development remains poorly understood. The gonad in C. elegans exhibits a mirror-symmetric structure guided by the migration of distal tip cells (DTCs), which result from asymmetric divisions of somatic gonadal precursors (SGPs; Z1 and Z4). We found that the polarity of Z1 and Z4, which possess mirror-symmetric orientation, is controlled by the redundant functions of the LIN-17/Frizzled receptor and three Wnt proteins (CWN-1, CWN-2, and EGL-20) with distinct functions. In lin-17 mutants, CWN-2 promotes normal polarity in both Z1 and Z4, while CWN-1 promotes reverse and normal polarity in Z1 and Z4, respectively. In contrast, EGL-20 inhibits the polarization of both Z1 and Z4. In lin-17; egl-20 cwn-2 triple mutants with a polarity reversal of Z1, DTCs from Z1 frequently miss-migrate to the posterior side. Our further analysis demonstrates that the mis-positioning of DTCs in the gonad due to the polarity reversal of Z1 leads to mis-migration. Similar mis-migration was also observed in cki-1(RNAi) animals producing ectopic DTCs. These results highlight the role of Wnt signaling in coordinating the production and migration of DTCs to establish a mirror-symmetric organ.

developmental biology↗