First published online June 25, 2007
Development 134, 1402e (2007)
© The Company of Biologists Limited
Hedgehog's fantom
Mice with the fused toes (Ft) mutation - a 1.6 Mb chromosomal
deletion encompassing six genes - exhibit phenotypes reminiscent of disrupted
Hedgehog (Hh) signalling. Vierkotten et al. have individually knocked out
these genes in mice to identify which one is involved in Hh signalling. On
p. 2569, they reveal
that the loss of fantom (Ftm) accounts for most defects in
Ft mice. Importantly, they report that Ftm localises to the ciliary
basal body where it functions as a novel component of cilia-related Hh
signalling - regulating the Gli3 activator (Gli3A) to processed Gli3 repressor
(Gli3R) ratio (Gli transcription factors act downstream of Hh). In
Ftm mutant mice, Gli3 levels increase; however, it remains
unprocessed, altering the ratio of Gli3A:Gli3R and consequently Hh
transcriptional output. Interestingly, Ftm is not required for cilia assembly;
however, cilia numbers are reduced where morphogenetic processes occur and
thus cilia-coupled signalling might be required for cilia maintenance. In
Drosophila, Hh signalling occurs independently of cilia;
unsurprisingly, a fly Ftm homologue hasn't been identified.
Related articles in Development:
- Ftm is a novel basal body protein of cilia involved in Shh signalling
- Jeanette Vierkotten, Renate Dildrop, Thomas Peters, Baolin Wang, and Ulrich Rüther
Development 2007 134: 2569-2577.
[Abstract]
[Full Text]
