The function and expansion of the Patched- and Hedgehog-related homologs in C. elegans

Abstract

The Hedgehog (Hh) signaling pathway promotes pattern formation and cell proliferation in Drosophila and vertebrates. Hh is a ligand that binds and represses the Patched (Ptc) receptor and thereby releases the latent activity of the multipass membrane protein Smoothened (Smo), which is essential for transducing the Hh signal. In Caenorhabditis elegans, the Hh signaling pathway has undergone considerable divergence. Surprisingly, obvious Smo and Hh homologs are absent whereas PTC, PTC-related (PTR), and a large family of nematode Hh-related (Hh-r) proteins are present. We find that the number of PTC-related and Hh-r proteins has expanded in C. elegans, and that this expansion occurred early in Nematoda. Moreover, the function of these proteins appears to be conserved in Caenorhabditis briggsae. Given our present understanding of the Hh signaling pathway, the absence of Hh and Smo raises many questions about the evolution and the function of the PTC, PTR, and Hh-r proteins in C. elegans. To gain insights into their roles, we performed a global survey of the phenotypes produced by RNA-mediated interference (RNAi). Our study reveals that these genes do not require Smo for activity and that they function in multiple aspects of C. elegans development, including molting, cytokinesis, growth, and pattern formation. Moreover, a subset of the PTC, PTR, and Hh-r proteins have the same RNAi phenotypes, indicating that they have the potential to participate in the same processes.

Thehedgehog-related genequa-1 is required for molting inCaenorhabditis elegans

“…In summary, all of the observed phenotypes are typical Mlt phenotypes that are also found in many other Mlt mutants. The Mlt phenotypes of qua-1(gk32) are consistent with the RNAi phenotypes that have been observed in large-scale RNAi screens Simmer et al, 2003;Frand et al, 2005;Zugasti et al, 2005). We repeated the qua-1(RNAi) feeding experiment and observed that the worms can have problems during ecdysis at any larval stage when RNAi treatment starts at the L1 stage.…”

“…In C. elegans, two patched genes, ptc-1 and ptc-3, as well as 24 patched-related genes exist (Kuwabara et al, 2000). RNAi analysis of these genes revealed that several, no- tably ptc-3, ptr-4, -16, -18, and -23 also cause strong Mlt phenotypes when knocked down (Zugasti et al, 2005). It is feasible that QUA-1 interacts directly with some of these Ptc or Ptr proteins, which may be involved in facilitating secretion of QUA-1.…”

“…A large group of extracellular matrix proteins and secreted enzymes contribute to the new cuticle or regulate release of the old one (Frand et al, 2005). In addition, a recent functional genomic study of C. elegans patched (ptc), patched-related (ptr), and hedgehog-related genes revealed that several of the hedgehogrelated genes including qua-1 are involved in molting (Zugasti et al, 2005).…”

A hedgehog homolog is involved in muscle formation and organization of Sepia officinalis (mollusca) mantle

“…By contrast, when Hh binds to Ptc, Smo inhibition is released and Hh signal is transduced within the target cell. ptc, found in Drosophila, in nematods (Zugasti et al, 2005) and in vertebrates as well Hahn et al, 1996;Marigo et al, 1996), is itself a target gene of hh signalling.…”

Greased hedgehogs: New links between hedgehog signaling and cholesterol metabolism

“…(29) They are, however, conspicuously absent in C. elegans, probably because its rigid pattern of differentiation can dispense with morphogen gradients. (30) Only some evolutionary remnants, in the form of hedgehog-related genes, remain detectable in the C. elegans genome. (31) The cascade of molecular events leading from Hh processing to signal reception at the target cell are also widely shared among animals.…”