CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility

Weidemann, Marina; Schuster-Gossler, Karin; Stauber, Michael; Wrede, Christoph; Hegermann, Jan; Ott, Tim; Boldt, Karsten; Beyer, Tina; Serth, Katrin; Kremmer, Elisabeth; Blum, Martin; Ueffing, Marius; Gossler, Achim

doi:10.1242/dev.139626

Cited by 22 publications

(12 citation statements)

References 71 publications

(72 reference statements)

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“…All of these candidates were co-expressed with Foxj1 throughout embryonic development in mouse and frog, including the LRO (mouse and frog), MCCs of the ependyma (mouse and frog), airways (mouse) and larval skin (frog) as well as sperm cells (mouse). These genes were found to have distinct context-and species-specific functions in motile cilia (Beckers et al, 2018;Weidemann et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The FOXJ1 target Cfap206 is required for sperm motility, mucociliary clearance of the airways and brain development

et al. 2020

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Cilia are complex cellular protrusions consisting of hundreds of proteins. Defects in ciliary structure and function, many of which have not been characterised molecularly, cause ciliopathies: a heterogeneous group of human syndromes. Here, we report on the FOXJ1 target gene Cfap206, orthologues of which so far have only been studied in Chlamydomonas and Tetrahymena. In mouse and Xenopus, Cfap206 was co-expressed with and dependent on Foxj1. CFAP206 protein localised to the basal body and to the axoneme of motile cilia. In Xenopus crispant larvae, the ciliary beat frequency of skin multiciliated cells was enhanced and bead transport across the epidermal mucociliary epithelium was reduced. Likewise, Cfap206 knockout mice revealed ciliary phenotypes. Electron tomography of immotile knockout mouse sperm flagella indicated a role in radial spoke formation reminiscent of FAP206 function in Tetrahymena. Male infertility, hydrocephalus and impaired mucociliary clearance of the airways in the absence of laterality defects in Cfap206 mutant mice suggests that Cfap206 may represent a candidate for the subgroup of human primary ciliary dyskinesias caused by radial spoke defects.

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Section: Introductionmentioning

confidence: 99%

The FOXJ1 target Cfap206 is required for sperm motility, mucociliary clearance of the airways and brain development

et al. 2020

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“…4 B). Additionally, there is one stop gained (rs73600054) in a cilium and flagella related gene ( CFAP157 ) [Weidemann et al, 2016] and one lost (rs80336323) in PSPN (persephin neurothropic factor).…”

Section: Resultsmentioning

confidence: 99%

Modern human alleles differentially regulate gene expression across brain regions: implications for brain evolution

Andirkó

Boeckx

2019

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8The high-quality sequence of the genomes of our extinct relatives, Ne-9 anderthals and Denisovans, became recently public. At the same time, 10 we have seen the emergence of big databases of modern human genetic 11 variation. However, linking human genetic variation, neuronal phenotypes 12 and, eventually, behaviour, is only possible if we understand how variation 13 and genetic regulation interact. We used two publicly available datasets, 14 the GTEX cis-eQTL database (v7) and a catalog of high-frequency Homo 15 Sapiens specific alleles relative to the Neanderthals and Denisovan se-16 quences, to understand how high-frequency Homo Sapiens derived alleles 17 affect gene expression regulation. The resulting dataset shows that genes 18 associated with brain development are affected by Homo sapiens-specific 19 eQTL in brain areas key in human evolution such as the cerebellum. We 20 also show that some of these eQTL overlap significantly with putative 21 regions of positive selection relative to archaic humans [Peyrégne et al., 22 2017]. Additionally, we tested whether any of the variants are associated 23 with clinical conditions in modern human populations. These findings can 24 inform future experimental work and enrich current venues of research of 25 the Homo Sapiens brain evolution, such as the relationship between clini-26 cal and evolutionary research and the recent expansion of the cerebellum 27 in Homo Sapiens [Gunz et al., 2010].28 Keywords-Human evolution, eQTL, brain evolution 29 and Boeckx, 2019]). 75 Our results show differential regulation by derived cis-eQTLs in key brain 76 areas and circuits that are claimed to have changed significantly during the 77 emergence of Homo sapiens, such as the cerebellum and olfactory signalling 78 pathway [Bastir et al., 2011]. We also found genetic regulation of cellular pro-79 cesses that can potentially impact neurodevelopment and disease, such as fo-80 late one-carbon metabolism, aerobic glycolysis regulation, cell-cell adhesion and 81 regulation of cytoskeleton dynamics. Some of these processes, such as aerobic 82 glycolysis, have already been discussed in other studies in the context of human 83 evolution and human-specific diseases such as Alzheimer's Disease [Bufill et al., 84 2011]. While we limited the scope of our study to brain tissue, we found as 85 well eQTLs associated with neural crest cell development and the craniofacial 86 complex. This is of special interest, as the Homo sapiens face has a distinct re-87 tracted profile compared to that of archaic humans [Lacruz et al., 2019]. Some 88 of the genes that affect brain development might exert an influence in adjacent 89 tissues [Boeckx, 2017]. 90 Since the eQTLs affect genes previously identified as under selective sweep in 91 modern humans relative to archaic humans, we tested whether the eQTLs affect 92 128 2015]. In this case, the effect of an eQTL is understood as the relative gene 129 expression difference between the minor, ancestral allele and the high-frequency 130 derived allele. As shown ...

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“…As discussed, the latter three genes have been implicated in female reproduction. FOXJ1 is a key transcription factor for the formation of motile cilia in human (Lyons et al 2006), mice and xenopus (Weidemann et al 2016). Immotile-cilia syndrome has been associated with male and female infertility in humans as motile cilia are critical in propelling ova along the fallopian tube while motility in sperm flagellum is also critical for sperm function and successful fertilization (Afzelius and Eliasson 1983).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries)

et al. 2019

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Maximizing the number of offspring born per female is a key functionality trait in commercial-and/or subsistence-oriented livestock enterprises. Although the number of offspring born is closely associated with female fertility and reproductive success, the genetic control of these traits remains poorly understood in sub-Saharan Africa livestock. Using selection signature analysis performed on Ovine HD BeadChip data from the prolific Bonga sheep in Ethiopia, 41 candidate regions under selection were identified. The analysis revealed one strong selection signature on a candidate region on chromosome X spanning BMP15, suggesting this to be the primary candidate prolificacy gene in the breed. The analysis also identified several candidate regions spanning genes not reported before in prolific sheep but underlying fertility and reproduction in other species. The genes associated with female reproduction traits included SPOCK1 (age at first oestrus), GPR173 (mediator of ovarian cyclicity), HB-EGF (signalling early pregnancy success) and SMARCAL1 and HMGN3a (regulate gene expression during embryogenesis). The genes involved in male reproduction were FOXJ1 (sperm function and successful fertilization) and NME5 (spermatogenesis). We also observed genes such as PKD2L2, MAGED1 and KDM3B, which have been associated with diverse fertility traits in both sexes of other species. The results confirm the complexity of the genetic mechanisms underlying reproduction while suggesting that prolificacy in the Bonga sheep, and possibly African indigenous sheep is partly under the control of BMP15 while other genes that enhance male and female fertility are essential for reproductive fitness.

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CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility

Cited by 22 publications

References 71 publications

The FOXJ1 target Cfap206 is required for sperm motility, mucociliary clearance of the airways and brain development

The FOXJ1 target Cfap206 is required for sperm motility, mucociliary clearance of the airways and brain development

Modern human alleles differentially regulate gene expression across brain regions: implications for brain evolution

Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries)

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