Forkhead Transcription Factor Fd3F Cooperates with Rfx to Regulate a Gene Expression Program for Mechanosensory Cilia Specialization

Abstract

SummaryCilia have evolved hugely diverse structures and functions to participate in a wide variety of developmental and physiological processes. Ciliary specialization requires differences in gene expression, but few transcription factors are known to regulate this, and their molecular function is unclear. Here, we show that the Drosophila Forkhead box (Fox) gene, fd3F, is required for specialization of the mechanosensory cilium of chordotonal (Ch) neurons. fd3F regulates genes for Ch-specific axonemal dyneins and TRPV ion channels, which are required for sensory transduction, and retrograde transport genes, which are required to differentiate their distinct motile and sensory ciliary zones. fd3F is reminiscent of vertebrate Foxj1, a motile cilia regulator, but fd3F regulates motility genes as part of a broader sensory regulation program. Fd3F cooperates with the pan-ciliary transcription factor, Rfx, to regulate its targets directly. This illuminates pathways involved in ciliary specialization and the molecular mechanism of transcription factors that regulate them.

Generation of sensory hair cells by genetic programming with a combination of transcription factors

“…Another reason might be that the GPA combination can only induce a partial HC phenotype, lacking the activity of additional TFs that are crucial for late HC differentiation. By comparison with the Atonal-driven sensory program in Drosophila chordotonal (Ch) neurons (Newton et al, 2012), in which the TF Fd3F acts downstream of Atonal to regulate various genes required for the assembly of mechanosensory cilia, we note that various 'missing' iHC genes are homologs of Fd3F targets in Drosophila. These include Tekt1, Wdr63, Dnahc6 (Dnah6), Dnahc9 (Dnah9) and Dynlrb2, which are all involved in axonemal dynein assembly.…”

Switching on cilia: transcriptional networks regulating ciliogenesis

“…DYF-17, B9 and BBS proteins), the transition zone (NPH-1 and NPH-4) and the axoneme (DYF-1) fall into this category, as do components of the IFT machinery (e.g. IFT88/OSM-5, IFT172/OSM-1 and XBX-1) (Ansley et al, 2003;Ashique et al, 2009;Burghoorn et al, 2012;Efimenko et al, 2005;Haycraft et al, 2001;Ou et al, 2005;Phirke et al, 2011;Schafer et al, 2003;Signor et al, 1999;Williams et al, 2008;Winkelbauer et al, 2005 and Drosophila Nan and Iav) (Burghoorn et al, 2012;Dwyer et al, 1998;Efimenko et al, 2005;Newton et al, 2012). RFX factors are thought to orchestrate ciliary differentiation programs after a cell has become committed towards a particular fate.…”

Methods to Study Centrosomes and Cilia in Drosophila

“…Note: This table is not an exhaustive list of all centrosome and cilia components mapped. Due to space constrain, only references for mutants and/or markers for each gene are mentioned in the list [15,16,19,21,31,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Also, for more information about the genes visit www.flybase.org.…”