First published online April 30, 2007
Development 134, 1006e (2007)
© The Company of Biologists Limited
Targeting the targets of Hedgehog
Sonic hedgehog (Shh) is secreted during neural tube (NT) development from
the notochord to specify different progenitors in a concentration-dependent
manner through the activity of activator (GliA) and repressor (GliR) forms of
the Gli proteins. Andrew McMahon's group - using a combined genetic and
bioinformatics approach to identify novel Gli targets during NT patterning -
now suggest on p.
1977 that, surprisingly, GliA and GliR differ in their selection of
target binding sites. Gli1-directed chromatin immunoprecipitation products
were screened against genomic tiling arrays of putative Hedgehog targets
(predicted from transcriptional profiling studies) to reveal both known and
novel Shh-Gli targets, such as Nkx2.2 and Rab34,
respectively. These targets were then validated by bioinformatics, expression
studies in cell culture and transgenic experiments. Along the way, the authors
have developed an algorithm that improves current in silico target prediction
methods and the authors suggest that their approach could expand our
understanding of transcriptional regulation in other developmental
settings.
Related articles in Development:
- Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning
- Steven A. Vokes, Hongkai Ji, Scott McCuine, Toyoaki Tenzen, Shane Giles, Sheng Zhong, William J. R. Longabaugh, Eric H. Davidson, Wing H. Wong, and Andrew P. McMahon
Development 2007 134: 1977-1989.
[Abstract]
[Full Text]
