Refining Signaling Domains

Science Signaling  01 Sep 2009:
Vol. 2, Issue 86, pp. ec290
DOI: 10.1126/scisignal.286ec290

Cilia are required for Hedgehog (Hh) signaling in the mouse but not in the fruit fly, and it has been suggested that Wnt signaling in the mouse may also require cilia. The requirement for cilia in Hh and Wnt signaling in zebrafish has been unclear because mutants lacking zygotically contributed cilia components transiently produce cilia in the early embryo, presumably due to the persistence of maternally contributed cilia components. Huang and Schier addressed this question by examining Hh and Wnt signaling in MZovl embryos, which lack both maternal and zygotic oval, the gene that encodes Ift88, an intraflagellar transport protein required for cilia formation. By morphological and immunohistochemical criteria, MZovl embryos lacked cilia in all cell types at all stages of development and showed developmental defects similar to those of Hh signaling mutants. The MZovl phenotype was not consistent with defects in either canonical or noncanonical Wnt signaling, and expression of Wnt target genes in MZovl embryos was normal. RNA in situ analysis indicated that the abundance of transcripts from Hh-activated target genes was reduced in MZovl embryos but that the spatial domains in which they were expressed were expanded. Expression of cell fate markers indicated that neural and muscle cell types specified in regions with relatively high Hh signaling were lost in MZovl embryos, whereas cell types specified in regions with relatively low Hh signaling occupied an expanded area. Whereas Hh signaling is severely reduced or absent in mouse embryos lacking cilia, spatially restricted domains of high Hh signaling were lost and replaced by diffuse domains of lower Hh signaling in fish embryos lacking cilia. The authors attribute the differences between the requirements for cilia in Hh signaling in mouse and fish to differences in the regulation of Gli transcription factors, the activities of which are modulated by Hh signaling. These findings, together with reports using frog and chick models, imply that the requirement for cilia in Hh signaling upstream of the Gli transcription factors is conserved throughout the vertebrates but that loss of cilia can affect Hh signaling differently in different species.

P. Huang, A. F. Schier, Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia. Development 136, 3089–3098 (2009). [Abstract] [Full Text]