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Sci. Signal., 3 November 2009
Vol. 2, Issue 95, p. ra70
[DOI: 10.1126/scisignal.2000602]
RESEARCH ARTICLES
The Rfx4 Transcription Factor Modulates Shh Signaling by Regional Control of Ciliogenesis
Amir M. Ashique1,
Youngshik Choe2,
Mattias Karlen3,
Scott R. May4,
Khanhky Phamluong1,
Mark J. Solloway1,
Johan Ericson3, and
Andrew S. Peterson1*
1 Department of Molecular Biology, Genentech, South San Francisco, CA 94080, USA. 2 Department of Neurology, University of California at San Francisco, San Francisco, CA 94158, USA. 3 Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm SE-171 77, Sweden. 4 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92186, USA.
Abstract:
Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, we describe an Rfx4L298P mouse mutant with distinct dorsoventral patterning defects in the ventral spinal cord and telencephalon due to aberrant Sonic hedgehog (Shh) signaling and Gli3 activity. We find that Ift172, which encodes an intraflagellar transport protein necessary for ciliogenesis, is a direct transcriptional target of Rfx4, and the decrease in its expression in the developing telencephalon and spinal cord of Rfx4L298P mutants correlates with defects in patterning and cilia formation. Our data indicate that Rfx4 is a regionally specific transcriptional regulator of ciliogenesis and thus is also a regionally specific modulator of Shh signaling during development of the central nervous system.
* To whom correspondence should be addressed. E-mail: peterson.andrew{at}gene.com
Citation: A. M. Ashique, Y. Choe, M. Karlen, S. R. May, K. Phamluong, M. J. Solloway, J. Ericson, A. S. Peterson, The Rfx4 Transcription Factor Modulates Shh Signaling by Regional Control of Ciliogenesis. Sci. Signal.2, ra70 (2009).
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