Gopal, S.; Farley, J. K.; Schwalbe, M.; Forsberg, F.; Amran, A.

Hedgehog (Hh) signaling is essential for embryonic development and tissue homeostasis in several organisms. However, Caenorhabditis elegans lacks canonical Hh signaling due to the absence of key components, such as smoothened (SMO) and 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 gonads 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 germline. Disruption of actin-regulating genes impairs germ cell cycle progression and reduces germ cell numbers, indicating that cytoskeletal integrity is critical for maintaining the germline. 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 the loss of Patched function can be rescued by modulating dietary cholesterol. Together, our findings reveal a role for Patched receptors in regulating germline architecture and germ cell development indirectly through a cholesterol-sensitive pathway, offering insights into how metabolic cues influence the organization of complex tissues and cells.