title: The Rfx4 transcription factor modulates Shh signaling by regional control of ciliogenesis.
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 Rfx4(L298P) 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 Rfx4(L298P) 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.
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ashique
authors.forename: Youngshik
authors.initials: Y
authors.lastname: Choe
authors.forename: Mattias
authors.initials: M
authors.lastname: Karlen
authors.forename: Scott R
authors.initials: SR
authors.lastname: May
authors.forename: Khanhky
authors.initials: K
authors.lastname: Phamluong
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Solloway
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Peterson
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000254:growth & development; D002923:Cilia; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D013116:Spinal Cord; D013687:Telencephalon; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D000071701:Regulatory Factor X Transcription Factors; C479564:Rfx4 protein, mouse; C465570:Shh protein, mouse; D014157:Transcription Factors