Conservation of Nuclear Receptor DAF-12 with Evidence for Ligand Diversification in Plant-Parasitic Nematodes
- 1University of Texas Southwestern Medical Center
Abstract
Plant-parasitic nematodes cause extensive crop losses that threaten global food security and create substantial economic hardship, yet strategies for their control remain limited. Although plant-parasitic nematodes have life cycles that mirror those of their free-living and animal-parasitic relatives, comparatively little is known about the signals that drive life-cycle progression. Dafachronic acids (DAs) are steroid hormones that control life cycle by activating DAF-12 nuclear receptors in Caenorhabditis elegans and animal-parasitic nematodes. To define whether an analogous pathway exists in plant-parasitic nematodes, we investigated the responsiveness of DAF-12 orthologs from six plant-parasitic nematode species to {Delta}7-DA, an endogenous DAF-12 ligand in C. elegans and several animal-parasitic nematodes. We find that whereas some plant-parasitic nematode receptors are activated by {Delta}7-DA, others are not. Structural modeling of all six ligand-binding domains, together with docking of {Delta}7-DA into each model, indicates that responsiveness is governed by a combinatorial ligand-recognition network surrounding the ligand carboxylate rather than by any single contact residue. We further demonstrate that egg and second-stage juvenile extracts from the soybean cyst nematode, Heterodera glycines, lack detectable DA but contain distinct lipophilic fractions that activate its DAF-12 ortholog. Together, these findings suggest that many plant-parasitic nematodes utilize endogenous DAF-12 ligands that are structurally distinct from DA. Uncovering modulators of this pathway could lead to new strategies to combat nematode-driven crop loss.
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BibTeX
@misc{liu2026conservation,
title = {{Conservation of Nuclear Receptor DAF-12 with Evidence for Ligand Diversification in Plant-Parasitic Nematodes}},
author = {Y. Liu and C.-W. Fan and Z. Wang and G. Wendt and L. G. Zacharias and J. G. McDonald and Y. Li and S.-Y. Shen and H. E. Xu and J. J. Collins and S. A. Kliewer and M. G. Mitchum and D. J. Mangelsdorf and T. P. Mathews},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.748874},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.748874v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Conservation of Nuclear Receptor DAF-12 with Evidence for Ligand Diversification in Plant-Parasitic Nematodes
AU - Y. Liu
AU - C.-W. Fan
AU - Z. Wang
AU - G. Wendt
AU - L. G. Zacharias
AU - J. G. McDonald
AU - Y. Li
AU - S.-Y. Shen
AU - H. E. Xu
AU - J. J. Collins
AU - S. A. Kliewer
AU - M. G. Mitchum
AU - D. J. Mangelsdorf
AU - T. P. Mathews
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.748874
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.748874v1
AB - Plant-parasitic nematodes cause extensive crop losses that threaten global food security and create substantial economic hardship, yet strategies for their control remain limited. Although plant-parasitic nematodes have life cycles that mirror those of their free-living and animal-parasitic relatives, comparatively little is known about the signals that drive life-cycle progression. Dafachronic acids (DAs) are steroid hormones that control life cycle by activating DAF-12 nuclear receptors in Caenorhabditis elegans and animal-parasitic nematodes. To define whether an analogous pathway exists in plant-parasitic nematodes, we investigated the responsiveness of DAF-12 orthologs from six plant-parasitic nematode species to {Delta}7-DA, an endogenous DAF-12 ligand in C. elegans and several animal-parasitic nematodes. We find that whereas some plant-parasitic nematode receptors are activated by {Delta}7-DA, others are not. Structural modeling of all six ligand-binding domains, together with docking of {Delta}7-DA into each model, indicates that responsiveness is governed by a combinatorial ligand-recognition network surrounding the ligand carboxylate rather than by any single contact residue. We further demonstrate that egg and second-stage juvenile extracts from the soybean cyst nematode, Heterodera glycines, lack detectable DA but contain distinct lipophilic fractions that activate its DAF-12 ortholog. Together, these findings suggest that many plant-parasitic nematodes utilize endogenous DAF-12 ligands that are structurally distinct from DA. Uncovering modulators of this pathway could lead to new strategies to combat nematode-driven crop loss.
ER -