Patched controls cell cycle and tissue architecture in C. elegans gonad

Hedgehog (Hh) signaling is essential for embryonic development and tissue homeostasis in organisms. However, Caenorhabditis elegans lacks canonical Hh signaling due to the absence of key components, such as smoothened (SMO) and obvious Hh ligands. Despite this, C. elegans retains Patched homologs, ptc-1 and ptc-3, which have specialized independent functions. Although ptc-1 is predominantly expressed in the germ line and ptc-3 in somatic tissues, we demonstrate that both genes are required to maintain germ cell populations and proper actin cytoskeletal architecture in the progenitor zone of the germ line. Disruption of actin-encoding genes impairs germ cell S-phase and reduces the number of cells in the progenitor zone, indicating that cytoskeletal integrity is critical for maintaining the germ line. Furthermore, defects observed upon loss of Patched function are linked to disruptions in cholesterol metabolism. We show that the phenotypes observed in the gonads due to dietary cholesterol changes can be modulated through Patched receptors. Together, our findings reveal a role for Patched receptors in regulating gonad architecture and germ cell development through cholesterol-sensitive functions, offering insights into how metabolic cues influence the organization of complex tissues.