Sensory structures are often composed of neurons extending their dendrites through a lumen formed by ensheathing epithelia or glia. We have been studying the development of the C. elegans amphid as a model system for sensory organ formation. Previously, we showed that
daf-6 is required for lumen formation by glial cells of the amphid [1]. In
daf-6 mutants, a lumen is not generated, and the ciliated sensory dendrites of the amphid become trapped in large vacuoles within the sheath glia.
daf-6 encodes a Patched-related protein that localizes to the luminal surfaces of the amphid channel, as well as to other tubes, including the excretory cell, vulva, and intestine. Whereas
daf-6 animals are defective only in amphid lumen morphogenesis, animals mutant for both
daf-6 and the Dispatched gene
che-14 exhibit defects in all tubular structures that express
daf-6. Furthermore, in mutants with defective sensory cilia, DAF-6 localization in the amphid is disrupted, and the amphid channel is malformed. Thus, lumen formation in the amphid may be orchestrated by neuronal cues that regulate the localization and function of DAF-6 and CHE-14. To further elucidate the role of
daf-6 in amphid lumen morphogenesis, we performed a genetic screen for suppressors of the dye-filling defect of
daf-6(
e1377) animals. One of these suppressors is an allele of the NLK/MAPK homologue
lit-1.
lit-1 is part of a MAPK module involved in the regulation of non-canonical Wnt signaling pathways that govern various cell fate decisions; however, mutations in
lit-1 do not affect glial cell specification.
lit-1 is expressed in many cells, including amphid glia and vulval cells. Heat shock studies as well as serial section EM of
daf-6 embryos revealed that
daf-6 functions during amphid channel formation. Consistent with this, expression of the
lit-1 cDNA by an embryonic amphid glia promoter rescues the suppression of
daf-6. Interestingly,
lit-1 enhances the amphid and vulval defects of
che-14 mutants, consistent with a model in which opposing activities of
daf-6 and
che-14 impinge on
lit-1 to promote optimal
lit-1 activity. Our results suggest a novel interaction between components of the Hedgehog and Wnt signaling pathways. Interestingly, studies of Wnt5a signaling in vertebrates suggest the possibility of similar interactions during mammary duct, vascular and airway tubulogenesis [2,3].