Work

HDAC1/2-mediated repression of Wnt receptor expression orients asymmetric division polarity in Caenorhabditis elegans

Year: 2026

Type: article

Abstract: Asymmetric cell division generates distinct daughter cells essential for tissue development, yet the mechanisms orienting division polarity within tissues remain incompletely understood. Here, we uncover a role for chromatin-mediated transcriptional repression in controlling polarity orientation during asymmetric division of Caenorhabditis elegans epidermal stem cells, known as the seam cells. Tissue-specific loss of the class I histone deacetylase hda-1, homologous to mammalian HDAC1/2, causes polarity reversals and reduces molecular asymmetry between daughter cells. Using Targeted DamID, we identify the Wnt receptors lin-17 (frizzled homologue) and cam-1 (Ror homologue) as key targets. Single-molecule fluorescence in situ hybridisation reveals opposing expression gradients along the body axis, with cam-1 enriched anteriorly and lin-17 posteriorly. In hda-1 mutants, both receptors are upregulated and differences between seam cells are flattened. Overexpression of either receptor alone is sufficient to reproduce the polarity reversals, while co-overexpression produces additive effects. The polarity phenotype is independent of the canonical NuRD and SIN3 complexes, suggesting that HDA-1 acts through an alternative mechanism. These findings link histone deacetylase activity to Wnt receptor expression and suggest that graded receptor expression may provide cues that orient asymmetric division polarity.

Source: Development

DOI: 10.1242/dev.205658