InteractiveFly: GeneBrief

forkhead domain 3F: Biological Overview | References

BIOLOGICAL OVERVIEW

Cilia 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. This study shows 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 (Newton, 2010).

The cilium commonly constitutes a cell's organelle for environmental sensing in a wide variety of contexts, from developmental signaling pathways (such as Sonic hedgehog) to the specialized receptor processes in sense organs of various sensory modalities (Ishikawa, 2011). In other situations, cilia are motile and play many roles connected to fluid movement in the airways, CNS, oviduct, and embryonic node. Despite this structural and functional diversity, cilia share a highly conserved pathway of ciliogenesis, involving basal body docking, axoneme extension, intraflagellar transport (IFT), and ciliary membrane assembly (Silverman, 2009). A major question is how this common assembly program is adapted and modified with cell-specific variations to generate cilia diversity (Silverman, 2009). It is likely that such specialization requires cell-type-specific gene expression programs, but little is known of the nature of these programs or of the transcription factors that regulate them (Newton, 2010).

In metazoans ciliogenesis broadly depends on regulatory factor X (Rfx: see Drosophila Rfx) transcription factors (Chu, 2010). Their targets are well characterized in functional and bioinformatic studies on C. elegans and Drosophila, and include genes required for “core” ciliogenesis processes such as anterograde IFT and membrane assembly. If Rfx is required broadly for ciliogenesis, what regulates cilium specialization? In fact Rfx targets include genes restricted to subtypes of ciliated cell, but it is not clear how it regulates such genes. It is speculated that Rfx cooperates with cell-type-specific factors (Silverman, 2009; Thomas, 2010), but the nature of this cooperation is uncharacterized (Newton, 2010).

Few cell-type-specific regulators of ciliogenesis have been characterized. The most well known are members of the FoxJ subfamily. In vertebrates, Foxj1 has been associated particularly with the differentiation of motile ciliated cell types (Brody, 2000; Jacquet, 2009; Stubbs, 2008; Yu, 2008). For instance, Foxj1 knockout mice have left-right asymmetry and airway defects (Brody, 2000). Target gene analyses have shown that Foxj1 regulates, directly or indirectly, many genes linked to ciliary motility, including axonemal dyneins, but not core ciliogenesis, such as IFT factors (Jacquet, 2009; Stubbs, 2008; Thomas, 2010; Yu, 2008). However, very little is known of its molecular mode of action or its relationship with Rfx function (Newton, 2010).

In Drosophila the only somatic cells with cilia are bipolar sensory neurons, which have specialized ciliary dendrites for sensory reception and transduction. Different classes of such neurons have ciliary dendrites that have different morphologies, express different sets of receptor molecules, and respond to different sensory modalities. These neurons present a useful model for investigating how ciliary diversity arises. External sensory (ES) neurons have a short connecting cilium leading to a distal sensory process with an irregular core of microtubules. In contrast, proprioceptive and auditory chordotonal (Ch) neurons have a long sensory cilium with a well-defined 9+0 axoneme (Eberl, 2000; Kernan, 1994). The Ch cilium has several unique specializations. First, its mechanosensory transduction mechanism uniquely involves TRPV (transient receptor potential) channels encoded by nanchung (nan) and inactive (iav). Second, it can be motile. In the auditory Ch neurons of Johnston's organ in the antenna, motility arises from the interplay between transduction channels and adaptation motors (possibly axonemal dyneins). Sensory-induced motility is thought to underlie a mechanical amplification mechanism to increase auditory sensitivity. Third, the Ch neuron cilium is divided by a ciliary dilation into functionally distinct proximal (motile) and distal (sensory) zones (Newton, 2010).

This study asked, therefore, what regulates gene expression for Ch neuron-specific ciliary specialization. Rfx is expressed in and required for ciliogenesis in both ES and Ch neurons, whereas Foxj1 homologs are reportedly absent from Drosophila. It was recently reported, however, that the Fox gene, fd3F, is required for Ch neuron function (Cachero, 2011). Here, we show that fd3F does not regulate ciliogenesis per se but directly regulates the genes required for aspects of Ch ciliary specialization. It appears that Fd3F cooperates closely with Rfx to regulate this Ch-specific cohort of genes and, therefore, it acts as a cell-type-specific modulator of Rfx target gene specificity. Comparison with Foxj1 and its target genes suggests that fd3F is a highly diverged relative of Foxj1 (Newton, 2010).

This study shows that Fd3F is a cell-type-specific transcriptional regulator of ciliary sensory specialization. It is exclusively expressed in mechanosensory Ch neurons where it regulates aspects of Ch neuron ciliogenesis and ciliary function. Fd3F is not a Ch neuron identity factor or 'master regulator' of Ch neuron differentiation: neural differentiation and ciliogenesis occur largely normally in fd3F mutant Ch neurons as attested by general morphology, and many Ch-specific genes are fd3F independent. Instead, fd3F regulates a program of gene expression for mechanosensory specialization that is unique to Ch neuron cilia and is absolutely required for their response to sensory stimulation. Specifically, fd3F targets are concerned with the structurally and functionally distinct ciliary zones of Ch neuron dendrites: fd3F regulates genes for both the machinery for construction and delineation of the zones (retrograde transport) and the proteins that populate the specialized proximal motor zone (axonemal dyneins, tektin, TRPV proteins). fd3F mutation has two consequences: ciliary motility of JO neurons is lost (reflected by loss of mechanical amplification), and sensory transduction is lost (reflected by loss of electrical response to stimulus). Effects on sensory transduction are both direct (loss of TRPV expression) and indirect (disrupted localization of candidate force-gated channel, TRPN1). Loss of axonemal dyneins might underlie the loss of motility directly, or their role may be indirect through their potential function as adaptation motors in sensory transduction (Newton, 2010).

Mutation of fd3F does not lead to transformation of Ch cilium morphology to that expected for ES neurons—only motility and compartmentalization-related specializations are lost. Similarly, fd3F misexpression does not convert ES cilia to a Ch cilium morphology. It is suggested that ES and Ch neuron cilia are both specialized derivatives of a default 'nonspecialized' cilium structure, such that loss of fd3F results only in loss of specific Ch ciliary specializations. There may be other aspects of specialization regulated by other factors in both Ch neurons and other sensory neurons (Newton, 2010).

Consideration of fd3F target genes illuminates the outstanding question of how ciliogenesis pathways are modulated to produce specialized cilia. One might surmise that ciliary specialization requires subtype-restricted gene products. This is true to some extent, as exemplified by the TRPV proteins and axonemal dyneins. However, the current findings suggest that quantitative differences in gene expression between sensory neuron subtypes are also important for ciliary specialization. Compartmentalization of Ch cilia into specialized motile and sensory zones requires retrograde transport proteins (Eberl, 2000; Lee, 2008). The results suggest that a 'basal' level of retrograde transport is sufficient for ciliogenesis in all sensory neurons (as is present in ES neurons and fd3F mutant Ch neurons), but compartmentalization of the Ch cilium requires a higher level of activity, as is provided by fd3F regulation of the genes involved. Thus, a quantitative difference in gene expression programs might underlie a qualitative feature of Ch ciliary specialization. This can be seen as a variation of the idea that differences in IFT activity might contribute to ciliary specialization (Silverman, 2009; Newton, 2010 and references therein).

One model for transcriptional regulation of ciliary specialization is that Rfx is required for pan-ciliary gene expression, whereas other more restricted transcription factors regulate subtype-specific gene expression (Silverman, 2009). However, some targets of Rfx are expressed only in subsets of ciliated cells (Efimenko, 2005), raising the question of how a pan-ciliary factor can be responsible for subtype-specific gene expression (Silverman, 2009; Wang, 2010). Rfx is required for all ciliated neurons in Drosophila, but its target gene specificity is modulated in Ch neurons by fd3F. This suggests a general mechanism in which Rfx cooperates with cell-type-specific transcription factors to regulate the genes required for cilia diversification. Most fd3F/Rfx targets have a conserved X box/Fox motif combination, demonstrating that specificity factors (in this case Fd3F) may act in very close molecular cooperation with Rfx, perhaps entailing cooperative binding. Conversely, most if not all fd3F target genes are also Rfx dependent, such that Rfx appears to be an obligate cofactor of Fd3F. Interestingly, the X boxes associated with fd3F targets often do not conform to the classic palindromic Rfx binding site (e.g., GTTGCCATGGCAAC; Avidor-Reiss, 2004) but, instead, show a strong match in only one half-site (RGYAAC). Half-sites and modified (nonpalindromic) X box sites have been noted for a variety of other cilia genes and might be especially associated with cell-type-restricted targets (Efimenko, 2005; Piasecki, 2010; Newton, 2010 and references therein).

Interestingly, the same X box/Fox site combination is shared by both Ch-specific and Ch-enriched targets. Therefore, Fd3F acts as an obligatory cofactor of Rfx for Ch-specific genes, but for Ch-enriched genes it only enhances a basal level of Rfx-dependent regulation that is already existent in Ch and ES neurons. To extend the model above, Rfx regulates low-level retrograde transport activity sufficient for its 'basal' ciliogenesis role, whereas fd3F/Rfx regulate the higher activity in Ch neurons that is required for ciliary compartmentalization (Newton, 2010).

In being required for Ch cilium motility, fd3F has a strikingly similar role to vertebrate Foxj1 genes, albeit that Foxj1 mutation has wider phenotypic consequences due to the many roles performed by motile cilia in vertebrates. Is fd3F related to Foxj1? The FoxJ subfamily is ancient, but bioinformatic analyses previously detected no Drosophila or C. elegans orthologs, suggesting that FoxJ genes have been lost from ecdysozoans. Conversely, such analyses also failed to assign fd3F to any Fox subfamily. However, a recent comprehensive analysis of mosquito Fox genes tentatively placed fd3F and its mosquito equivalent in the FoxJ subfamily (Hansen, 2007). Although the sequence evidence is equivocal, this study suggests that fd3F is a highly diverged representative of the FoxJ subfamily (Newton, 2010).

Support for this relationship comes from consideration of target genes. Target gene analyses have indicated many candidate direct or indirect targets for Foxj1 in mouse and Xenopus (Jacquet, 2009; Stubbs, 2008). Several fd3F target genes are homologs of Foxj1-dependent genes in multiple vertebrate species (Thomas, 2010), including Dhc93AB (DNAH9 in human), CG9313 (WDR66), tektin-A (TEKT4), CG6971 (DNALI1), CG13930 (WDR78), Dhc62B (DNAH3), Dhc16F (DNAH6), CG10064 (WDR16), and CG34192 (DNALRB2). The shared targets are all directly concerned with motility, whereas retrograde transport genes are not Foxj1 targets in vertebrates. This suggests that regulation of axonemal motor genes is an ancestral function of Foxj1/fd3F, whereas regulation of retrograde transport was acquired later in the Drosophila lineage, coinciding with the emergence of distinct ciliary zones in the evolution of Ch neurons. Other fd3F target genes have no known function: it is suggested they provide a potential source of new ciliary motility genes (Newton, 2010).

Cilia are classically classified as either being sensory (primary) with a 9+0 microtubule axoneme or propulsive (motile) with a 9+2 axoneme. Ch cilia are 9+0 sensory cilia with a limited set of motility-related features that are intimately linked to the Ch sensory transduction mechanism. These cilia therefore differ greatly from most propulsive cilia. Several Foxj1-dependent cell types also bear 9+0 motile cilia somewhat reminiscent of those on Ch neurons. These include the mouse embryonic node, which is required for left-right asymmetry (Brody, 2000), related cells in Xenopus and zebrafish (e.g., Kupffer's vesicle), and long 9+0 cilia of the neural tube floor plate in zebrafish (Stubbs, 2008; Yu, 2008; Newton, 2010 and references therein).

In vertebrates, Rfx3 is required in many ciliated cells that also require Foxj1, including the mouse embryonic node, CNS ependymal cells, and chick neural tube floor plate. Moreover, in the embryonic node Rfx3 regulates genes involved not only with ciliogenesis but also with cilium mobility, and some Foxj1-dependent genes are also affected in Rfx3 mutants, including Dnahc9, the ortholog of Dhc93AB. This study suggests that Rfx3/Foxj1 may work in combination to regulate directly a subset of ciliary targets in the way this study has identified for Rfx/fd3F (Newton, 2010).

The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons

In neurogenesis, neural cell fate specification is generally triggered by proneural transcription factors. While the role of proneural factors in fate specification is well studied, the link between neural specification and the cellular pathways that ultimately must be activated to construct specialized neurons is usually obscure. High-resolution temporal profiling of gene expression reveals the events downstream of atonal proneural gene function during the development of Drosophila chordotonal (mechanosensory) neurons. Among other findings, this reveals the onset of expression of genes required for construction of the ciliary dendrite, a key specialization of mechanosensory neurons. This study determined that atonal activates this cellular differentiation pathway in several ways. Firstly, atonal directly regulates Rfx, a well-known highly conserved ciliogenesis transcriptional regulator. Unexpectedly, differences in Rfx regulation by proneural factors may underlie variations in ciliary dendrite specialization in different sensory neuronal lineages. In contrast, fd3F encodes a novel forkhead family transcription factor that is exclusively expressed in differentiating chordotonal neurons. fd3F regulates genes required for specialized aspects of chordotonal dendrite physiology. In addition to these intermediate transcriptional regulators, this study shows that Atonal directly regulates a novel gene, dilatory, that is directly associated with ciliogenesis during neuronal differentiation. This analysis demonstrates how early cell fate specification factors can regulate structural and physiological differentiation of neuronal cell types. It also suggests a model for how subtype differentiation in different neuronal lineages may be regulated by different proneural factors. In addition, it provides a paradigm for how transcriptional regulation may modulate the ciliogenesis pathway to give rise to structurally and functionally specialized ciliary dendrites (Cachero, 2011).

Numerous genetic and misexpression analyses in a range of organisms have shown that proneural factors influence a neuron's ultimate phenotype (including its subtype identity) at an early stage in its development. However, the nature of this influence on the cell biological processes of neuronal differentiation has remained obscure. This study bridges the gap between early specification by the proneural factor, ato, and the differentiation of Ch neurons. The current model in both Drosophila and vertebrates is that proneural factors activate two types of target gene during neural precursor specification: a common target set for shared neuronal properties and a unique target set for subtype-specific properties. The data suggest that such neuronal subtype differences are ultimately controlled by proneural factors in several ways: by the differential regulation of both specific and common intermediate transcription factors, which in turn regulate genes for aspects of neuronal structural and functional differentiation, and by direct regulation of potential differentiation genes (Cachero, 2011).

The proneural factors ato and sc commit cells to similar but distinct neural precursor fates: Ch and ES neurons are evolutionarily related cell types with similar but distinct structural and physiological properties. Notably, both are characterised by the possession of specialised ciliary-based dendrites. Thus, ciliogenesis is a key pathway that must ultimately be activated in sensory neurons subsequent to proneural factor function. However, there are important differences between the dendrites of Ch and ES neurons. Ch dendrites have a more prototypically organised axonemal structure and possess a characteristic ciliary dilation - a specialisation that separates the Ch ciliary dendrite into functionally distinct zones. Moreover, there is evidence for an active 'beat' of Ch cilia during sensory transduction. In general, ES dendrites appear reduced in structure: although a basal body and short axoneme are present, the tip of the dendrite consists of a 'tubular body' of irregularly packed microtubules. Thus the basic ciliogenesis pathway must be modulated differently in Ch and ES differentiation, and ultimately this must reflect a difference in function between ato and sc proneural factors. The ciliogenic regulator Rfx is expressed and required for both ES and Ch lineages, but it is more strongly and more persistently expressed in Ch lineages (the Ch-enriched pattern). This modulation of Rfx expression is at least partly due to differences in its regulation by proneural factors, since it appears to be a direct target of ato but not sc. This study hypothesises that differences in Rfx regulation by the proneural factors lead to differences in implementation of a core cilia biogenesis program, thereby directly linking early proneural factor function with key differences of neuronal morphology. Consistent with this idea, the data show that several known or predicted ciliogenesis genes also exhibit this Ch-enriched pattern, and some of these are predicted or known Rfx targets (Cachero, 2011).

In this view, the subtype differences between Ch and ES neurons are partly produced by quantitative differences in timing or level of expression of a common differentiation process, which ultimately depends on a qualitative difference in Rfx regulation by the proneural factors. A possible example of this is CG6129. This gene is a predicted Rfx target gene and is expressed in a Ch-enriched pattern (Laurenon, 2007). The homologous mouse protein (Rootletin) localises to the ciliary rootlet and is required for its formation. Thus Ch-enriched expression of CG6129 explains the presence of the ciliary rootlet in Ch neurons but not ES neurons. One prediction of this hypothesis is that overexpression of Rfx in ES neurons will upregulate Ch-enriched genes, and this is borne out by preliminary experiments that show an increase in CG6129 expression in ES neurons upon Rfx overexpression. It is notable that differences in IFT activity are proposed to underlie differences in ciliary morphology while RFX class factors have been associated with regulating genes for IFT in a variety of organisms. This work suggests that variations in Rfx expression level and timing should be explored as a possible factor in cilium diversity (Cachero, 2011).

fd3F fits the more conventional view of a proneural target gene that implements a subtype-specific program of differentiation. It is expressed downstream of ato uniquely in Ch neurons and regulates genes required for functional specialisation of the Ch ciliary dendrite. It is likely that Forkhead factors regulate specialisation of ciliogenesis in other organisms. In C. elegans, FKH-2 is expressed widely early in development but is also required specifically for ciliary specialisation of one type of sensory neuron. Foxj1 in mice, Xenopus, and zebrafish appears to be required for the motile cilia of the lung airway and embryonic node, but not for primary cilia. It remains to be determined whether fd3F regulates the machinery for the active beat that occurs in Ch dendrites as part of sensory transduction. Together, these studies of Rfx and fd3F extend the previously limited knowledge of the gene regulatory network underlying ciliogenesis and provide insight into how the core program may be modified to produce the highly specialised and diverse morphologies that cilia adopt for different functions (Cachero, 2011).

Previous to this study, little was known about how ato/sc proneural genes control the acquisition of Ch/ES subtype identity, except that regulation of the Cut homeodomain transcription factor is involved. Mutant and misexpression analyses show that cut is a fate selector switch for ES identity downstream of sc, but nothing is known of its mode of action or targets. Whereas Rfx and fd3F functions are likely to be confined to neuronal morphology, cut affects the identity of support cells too. As a fate switch in the entire lineage, it appears likely that cut is involved in high-level fate specification (like proneural genes) rather than regulating aspects of differentiation directly. However, it is also possible that cut may repress ciliogenesis genes in ES neurons, either directly or by repressing Rfx expression. It will be important to integrate cut into the Ch/ES gene regulatory network in the future (Cachero, 2011).

In the temporal expression profiling data, there is a steady increase in the number of known or suspected differentiation genes expressed in developing Ch cells. Many more are not expressed until after the analysis ends. Ciliogenesis is a highly intricate cellular process requiring the coordination of perhaps hundreds of genes and differences in expression onset may indicate prerequisite steps in the process of differentiation and ciliogenesis. A surprising observation was the significant number of ciliogenesis and differentiation genes that are expressed even at the earliest profiling time point. This is unexpected, since the earliest time point is predicted to be not only before differentiation but also even before cell divisions have generated the neurons. It is suggested that further analysis of expression timing may lead to insights into the cell biology of ciliogenesis. The early activation of differentiation genes may reflect the rapid pace of development in the Drosophila embryo. Thus, early expression of ciliogenesis genes may provide components that prime cells for rapid cilium assembly later once differentiation has been triggered. Along these lines, the findings mirror striking observations of retinal ganglion cells, whose rapid differentiation within 15 minutes of the exit from mitosis has been taken to imply that genes required in postmitotic cells must be transcribed before cell division. A more intriguing possibility is that early expression reflects an orderly time course for ciliogenesis that begins many hours before the final cell division. For example, unc is thought to be required for the conversion of the mitotic centriole to ciliogenic basal body, but this stuyd found that the mRNA and fusion protein are expressed even in SOPs, several cell divisions before terminal differentiation. Interestingly, in mammals newly replicated centrioles mature over two cell cycles. It is conceivable that the sensory neuron basal body might similarly need time to mature (Cachero, 2011).

Since Rfx and some ciliogenesis genes are expressed in SOPs, what prevents ciliogenesis from being activated in the non-neuronal support cells? One possibility would be an extension of model recently proposed for the generation of support cell differences, in which Notch signalling between daughter cells confines the function of genes to one branch of the lineage. This would predict that ciliogenesis genes and/or Rfx are Notch target genes. Another possibility is that some of the gene products are asymmetrically segregated. Thirdly, ciliogenesis may not be triggered until one or more key gene products are produced in the neuronal cell (Cachero, 2011).

As a corollary, it will be important to explore further the gene regulatory network underlying the temporal and cell-type differences in ciliogenesis genes. Some early expressed differentiation genes are known or predicted Rfx targets (Laurenon, 2007). This gives a rationale for the early regulation of Rfx by ato in Ch lineages. However, in both C. elegans and D. melanogaster, Rfx regulates only a subset of ciliogenesis genes (notably, it does not regulate IFT-A genes). Further studies on ato target genes and the ciliogenesis regulatory network in sensory neurons will identify other important regulators. It remains to be determined how many differentiation genes are, like dila, direct targets of ato. Interestingly, vertebrate proneural factors are hypothesised to regulate directly the transition from cycling neural progenitor (or neural stem cell) to postmitotic differentiating neuron. Perhaps ato has retained some part of an ancestral proneural factor function in direct regulation of terminal differentiation despite the subsequent evolution of SOPs that must undergo several divisions before differentiating (Cachero, 2011).

Search PubMed for articles about Drosophila fd3F

Avidor-Reiss, T., et al. (2004). Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell 117: 527-539. PubMed ID: 15137945

Brody, S. L., et al. (2000). Ciliogenesis and left-right axis defects in forkhead factor HFH-4-null mice. Am. J. Respir. Cell Mol. Biol. 23: 45-51. PubMed ID: 10873152

Cachero, S., et al. (2011). The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons. PLoS Biol. 9 e1000568. PubMed ID: 21283833

Chu, J. S., Baillie, D. L., Chen, N. (2010). Convergent evolution of RFX transcription factors and ciliary genes predated the origin of metazoans. BMC Evol. Biol. 10: 130. PubMed ID: 20441589

Eberl, D. F., Hardy, R. W. and Kernan, M. J. (2000). Genetically similar transduction mechanisms for touch and hearing in Drosophila. J. Neurosci. 20: 5981-5988. PubMed ID: 10934246

Efimenko, E., et al. (2004). Analysis of xbx genes in C. elegans. Development 132: 1923-1934. PubMed ID: 15790967

Hansen, I. A., et al. (2007). Forkhead transcription factors regulate mosquito reproduction Insect Biochem. Mol. Biol. 37: 985-997. PubMed ID: 17681238

Ishikawa, H. and Marshall, W. F. (2011). Ciliogenesis: building the cell's antenna. Nat. Rev. Mol. Cell Biol. 12: 222-234. PubMed ID: 21427764

Jacquet, B. V., et al. (2009). FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain. Development 136: 4021-4031. PubMed ID: 19906869

Kernan, M., Cowan, D. and Zuker, C. (1994). Genetic dissection of mechanosensory transduction: mechanoreception-defective mutations of Drosophila. Neuron 12: 1195-1206. PubMed ID: 8011334

Lee, E. et al. (2008). An IFT-A protein is required to delimit functionally distinct zones in mechanosensory cilia. Curr. Biol. 18: 1899-1906. PubMed ID: 19097904

Newton, F. G., zur Lage, P. I., Karak, S., Moore, D. J., Göpfert, M. C. and Jarman, A. P. (2012). Forkhead transcription factor Fd3F cooperates with Rfx to regulate a gene expression program for mechanosensory cilia specialization. Dev. Cell 22(6): 1221-33. PubMed ID: 22698283

Piasecki, B. P., Burghoorn, J. and Swoboda, P. (2010). Regulatory Factor X (RFX)-mediated transcriptional rewiring of ciliary genes in animals. Proc. Natl. Acad. Sci. 107: 12969-12974. PubMed ID: 20615967

Silverman, M. A. and Leroux, M. R. (2009). Intraflagellar transport and the generation of dynamic, structurally and functionally diverse cilia. Trends Cell Biol. 19: 306-316. PubMed ID: 19560357

Stubbs, J. L., et al. (2008). The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nat. Genet. 40: 1454-1460. PubMed ID: 19011629

Thomas, J., et al. (2010). Transcriptional control of genes involved in ciliogenesis: a first step in making cilia. Biol. Cell 102: 499-513. PubMed ID: 20690903

Wang, J., Schwartz, H. T. and Barr, M. M. (2010). Functional specialization of sensory cilia by an RFX transcription factor isoform. Genetics 186: 1295-1307. PubMed ID: 20923979

Yu, X., et al. (2008). Foxj1 transcription factors are master regulators of the motile ciliogenic program. Nat. Genet. 40: 1445-1453. PubMed ID: 19011630

date revised: 25 July 2022

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