Evolutionarily Ancient Association of the FoxJ1 Transcription Factor with the Motile Ciliogenic Program

Abstract

It is generally believed that the last eukaryotic common ancestor (LECA) was a unicellular organism with motile cilia. In the vertebrates, the winged-helix transcription factor FoxJ1 functions as the master regulator of motile cilia biogenesis. Despite the antiquity of cilia, their highly conserved structure, and their mechanism of motility, the evolution of the transcriptional program controlling ciliogenesis has remained incompletely understood. In particular, it is presently not known how the generation of motile cilia is programmed outside of the vertebrates, and whether and to what extent the FoxJ1-dependent regulation is conserved. We have performed a survey of numerous eukaryotic genomes and discovered that genes homologous to foxJ1 are restricted only to organisms belonging to the unikont lineage. Using a mis-expression assay, we then obtained evidence of a conserved ability of FoxJ1 proteins from a number of diverse phyletic groups to activate the expression of a host of motile ciliary genes in zebrafish embryos. Conversely, we found that inactivation of a foxJ1 gene in Schmidtea mediterranea, a platyhelminth (flatworm) that utilizes motile cilia for locomotion, led to a profound disruption in the differentiation of motile cilia. Together, all of these findings provide the first evolutionary perspective into the transcriptional control of motile ciliogenesis and allow us to propose a conserved FoxJ1-regulated mechanism for motile cilia biogenesis back to the origin of the metazoans.

Switching on cilia: transcriptional networks regulating ciliogenesis

“…Furthermore, an in-depth study of the evolutionary history of foxj1 has clarified that foxj1 orthologs, like those of the RFX factors, are present throughout the unikonts, but the gene has been secondarily lost from certain lineages (Vij et al, 2012). The authors confirmed this bioinformatics-based analysis by demonstrating a functional association between FOXJ1 and motile ciliogenesis in the flatworm Schmidtea mediterranea (Vij et al, 2012).…”

“…Furthermore, an in-depth study of the evolutionary history of foxj1 has clarified that foxj1 orthologs, like those of the RFX factors, are present throughout the unikonts, but the gene has been secondarily lost from certain lineages (Vij et al, 2012). The authors confirmed this bioinformatics-based analysis by demonstrating a functional association between FOXJ1 and motile ciliogenesis in the flatworm Schmidtea mediterranea (Vij et al, 2012). Concurrently, work in Drosophila revealed that a forkhead box transcription factor, FD3F, is expressed in a set of proprioceptive and auditory neurons, the chordotonal neurons, which make long mechanosensory cilia that are partially motile (9+0, with dynein arms) (Cachero et al, 2011;Newton et al, 2012).…”

Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis and maintenance of axial patterning

“…To verify that the yki(RNAi) protonephridial defect was not attributed to defects in ciliogenesis, which can also cause an edema phenotype, we confirmed that the dorsal midline cilia and the ciliated ventral epithelium, as determined by normal locomotion, were not affected (supplementary material Fig. S3A; supplementary material Movies 1, 2) (Glazer et al, 2010;Rink et al, 2009;Vij et al, 2012).…”

Contrôle transcriptionnel des gènes ciliaires

“…Ce facteur est présent chez de nombreux eucaryotes et semble avoir évolué avec la présence de cils mobiles [22]. Aucun homologue n'est présent chez C. elegans qui ne possède pas de cils mobiles, ni chez Drosophila melanogaster.…”