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In contrast to the progress in understanding ciliogenesis and cilium function, we know less about the transcriptional regulation of ciliogenesis genes and how this regulatory program is modulated to generate diverse cilia. Drosophila sensory neurons have ciliary dendrites that are structurally and functionally specialised for receiving different sensory modalities. Time-course gene expression profiling of differentiating chordotonal (Ch) mechanosensory neurons allowed us to determine how Atonal, a proneural bHLH factor, regulates events leading to mechanosensory cilium formation and specialisation. Atonal regulates ciliogenesis via activation of two downstream transcription factors: the well-known cilia gene regulator, Rfx, and a novel factor of the Forkhead family (Fd3F). Rfx regulates a variety of ciliogenesis genes in all ciliated sensory neurons. In contrast, Fd3F is unique to Ch neurons, where it regulates a cohort of genes required for ciliary motility – a unique specialisation of Ch cilia in Drosophila and an essential part of the hearing mechanism. Among the targets of Fd3F are genes with human homologues linked to primary ciliary dyskinesia, a congenital condition resulting from defective ciliary motility. We provide evidence that Fd3F is a previously unrecognised orthologue of Foxj1, the so-called master regulator of motile ciliated cells in vertebrates. Interestingly, Fd3F and Rfx cooperate to regulate motility target genes directly via adjacent DNA binding sites, thus providing a mechanism for how Rfx can regulate genes for cilium specialisation in addition to ‘core’ ciliogenesis genes. Our study suggests how Foxj1 and Rfx factors may interact in vertebrates to generate ciliary diversity. http://www.ed.ac.uk/schools-departments/integrative-physiology/staff-profiles/andrew-jarman

Background Movement of cells, either as amoeboid individuals or in organised groups, is a key feature of organ formation. Both modes of migration occur during Drosophila embryonic gonad development, which therefore provides a paradigm for understanding the contribution of these processes to organ morphogenesis. Gonads of Drosophila are formed from three distinct cell types: primordial germ cells (PGCs), somatic gonadal precursors (SGPs), and in males, male-specific somatic gonadal precursors (msSGPs). These originate in distinct locations and migrate to associate in two intermingled clusters which then compact to form the spherical primitive gonads. PGC movements are well studied, but much less is known of the migratory events and other interactions undergone by their somatic partners. These appear to move in organised groups like, for example, lateral line cells in zebra fish or Drosophila ovarian border cells. Results We have used time-lapse fluorescence imaging to characterise gonadal cell behaviour in wild type and mutant embryos. We show that the homeodomain transcription factor Six4 is required for the migration of the PGCs and the msSGPs towards the SGPs. We have identified a likely cause of this in the case of PGCs as we have found that Six4 is required for expression of Hmgcr which codes for HMGCoA reductase and is necessary for attraction of PGCs by SGPs. Six4 affects msSGP migration by a different pathway as these move normally in Hmgcr mutant embryos. Additionally, embryos lacking fully functional Six4 show a novel phenotype in which the SGPs, which originate in distinct clusters, fail to coalesce to form unified gonads. Conclusion Our work establishes the Drosophila gonad as a model system for the analysis of coordinated cell migrations and morphogenesis using live imaging and demonstrates that Six4 is a key regulator of somatic cell function during gonadogenesis. Our data suggest that the initial association of SGP clusters is under distinct control from the movements that drive gonad compaction.

Background The regulation of proneural gene expression is an important aspect of neurogenesis. In the study of the Drosophila proneural genes, scute and atonal, several themes have emerged that contribute to our understanding of the mechanism of neurogenesis. First, spatial complexity in proneural expression results from regulation by arrays of enhancer elements. Secondly, regulation of proneural gene expression occurs in distinct temporal phases, which tend to be under the control of separate enhancers. Thirdly, the later phase of proneural expression often relies on positive autoregulation. The control of these phases and the transition between them appear to be central to the mechanism of neurogenesis. We present the first investigation of the regulation of the proneural gene, amos. Results Amos protein expression has a complex pattern and shows temporally distinct phases, in common with previously characterised proneural genes. GFP reporter gene constructs were used to demonstrate that amos has an array of enhancer elements up- and downstream of the gene, which are required for different locations of amos expression. However, unlike other proneural genes, there is no evidence for separable enhancers for the different temporal phases of amos expression. Using mutant analysis and site-directed mutagenesis of potential Amos binding sites, we find no evidence for positive autoregulation as an important part of amos control during neurogenesis. Conclusion For amos, as for other proneural genes, a complex expression pattern results from the sum of a number of simpler sub-patterns driven by specific enhancers. There is, however, no apparent separation of enhancers for distinct temporal phases of expression, and this correlates with a lack of positive autoregulation. For scute and atonal, both these features are thought to be important in the mechanism of neurogenesis. Despite similarities in function and expression between the Drosophila proneural genes, amos is regulated in a fundamentally different way from scute and atonal.