Control of ciliary transcriptional programs during spermatogenesis by antagonistic transcription factors
Curation statements for this article:-
Curated by eLife
eLife assessment
This study reports useful data suggesting the critical roles of two ancient proteins, XAP5 and XAP5L, in controlling the transcriptional program of ciliogenesis during mouse spermatogenesis. However, this study is considered incomplete because the data only partially support the conclusion. This work will be of interest to biomedical researchers who work on ciliogenesis and reproduction.
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
- Cell Biology (eLife)
Abstract
Existence of cilia in the last eukaryotic common ancestor (LECA) raises a fundamental question in biology: how the transcriptional regulation of ciliogenesis has evolved? One conceptual answer to this question is by an ancient transcription factor regulating ciliary gene expression in both unicellular and multicellular organisms, but examples of such transcription factors in eukaryotes are lacking. Previously, we showed that an ancient transcription factor XAP5 is required for flagellar assembly in Chlamydomonas . Here, we show that XAP5 and XAP5L are two conserved pairs of antagonistic transcription regulators that control ciliary transcriptional programs during spermatogenesis. Male mice lacking either XAP5 or XAP5L display infertility, as a result of meiotic prophase arrest and sperm flagella malformation, respectively. Mechanistically, XAP5 positively regulates the ciliary gene expression by activating the key regulators including FOXJ1 and RFX families during the early stage of spermatogenesis. In contrast, XAP5L negatively regulates the expression of ciliary genes via repressing these ciliary transcription factors during the spermiogenesis stage. Our results provide new insights into the mechanisms by which temporal and spatial transcription regulators are coordinated to control ciliary transcriptional programs during spermatogenesis.
Article activity feed
-
-
-
eLife assessment
This study reports useful data suggesting the critical roles of two ancient proteins, XAP5 and XAP5L, in controlling the transcriptional program of ciliogenesis during mouse spermatogenesis. However, this study is considered incomplete because the data only partially support the conclusion. This work will be of interest to biomedical researchers who work on ciliogenesis and reproduction.
-
Reviewer #1 (Public Review):
Summary:
Wang et al. generate XAP5 and XAP5L knockout mice and find that they are male infertile due to meiotic arrest and reduced sperm motility, respectively. RNA-Seq was subsequently performed and the authors concluded that XAP5 and XAP5L are antagonistic transcription factors of cilliogenesis (in XAP5-KO P16 testis: 554 genes were unregulated and 1587 genes were downregulated; in XAP5L-KO sperm: 2093 genes were unregulated and 267 genes were downregulated).
Strengths:
Knockout mouse models provided strong evidence to indicate that XAP5 and XAP5L are critical for spermatogenesis and male fertility.
Weaknesses:
The key conclusions are not supported by evidence. First, the authors claim that XAP5 and XAP5L transcriptionally regulate sperm flagella development; however, detailed molecular experiments related …
Reviewer #1 (Public Review):
Summary:
Wang et al. generate XAP5 and XAP5L knockout mice and find that they are male infertile due to meiotic arrest and reduced sperm motility, respectively. RNA-Seq was subsequently performed and the authors concluded that XAP5 and XAP5L are antagonistic transcription factors of cilliogenesis (in XAP5-KO P16 testis: 554 genes were unregulated and 1587 genes were downregulated; in XAP5L-KO sperm: 2093 genes were unregulated and 267 genes were downregulated).
Strengths:
Knockout mouse models provided strong evidence to indicate that XAP5 and XAP5L are critical for spermatogenesis and male fertility.
Weaknesses:
The key conclusions are not supported by evidence. First, the authors claim that XAP5 and XAP5L transcriptionally regulate sperm flagella development; however, detailed molecular experiments related to transcription regulation are lacking. How do XAP5 and XAP5L regulate their targets? Only RNA-Seq is not enough. Second, the authors declare that XAP5 and XAP5L are antagonistic transcription factors; however, how do XAP5 and XAP5L regulate sperm flagella development antagonistically? Only RNA-Seq is not enough. Third, I am concerned about whether XAP5 really regulates sperm flagella development. XAP5 is specifically expressed in spermatogonia and XAP5-cKO mice are in meiotic arrest, indicating that XAP5 regulates meiosis rather than sperm flagella development.
-
Reviewer #2 (Public Review):
In this study, Wang et al., report the significance of XAP5L and XAP5 in spermatogenesis, involved in transcriptional regulation of the ciliary gene in testes. In previous studies, the authors demonstrate that XAP5 is a transcription factor required for flagellar assembly in Chlamydomonas. Continuing from their previous study, the authors examine the conserved role of the XAP5 and XAP5L, which are the orthologue pair in mammals.
XAP5 and XAP5L express ubiquitously and testis specifically, respectively, and their absence in the testes causes male infertility with defective spermatogenesis. Interestingly, XAP5 deficiency arrests germ cell development at the pachytene stage, whereas XAP5L absence causes impaired flagellar formation. RNA-seq analyses demonstrated that XAP5 deficiency suppresses ciliary gene …
Reviewer #2 (Public Review):
In this study, Wang et al., report the significance of XAP5L and XAP5 in spermatogenesis, involved in transcriptional regulation of the ciliary gene in testes. In previous studies, the authors demonstrate that XAP5 is a transcription factor required for flagellar assembly in Chlamydomonas. Continuing from their previous study, the authors examine the conserved role of the XAP5 and XAP5L, which are the orthologue pair in mammals.
XAP5 and XAP5L express ubiquitously and testis specifically, respectively, and their absence in the testes causes male infertility with defective spermatogenesis. Interestingly, XAP5 deficiency arrests germ cell development at the pachytene stage, whereas XAP5L absence causes impaired flagellar formation. RNA-seq analyses demonstrated that XAP5 deficiency suppresses ciliary gene expression including Foxj1 and Rfx family genes in early testis. By contrast, XAP5L deficiency abnormally remains Foxj1 and Rfx genes in mature sperm. From the results, the authors conclude that XAP5 and XAP5L are the antagonistic transcription factors that function upstream of Foxj1 and Rfx family genes.
This reviewer thinks the overall experiments are performed well and that the manuscript is clear. However, the current results do not directly support the authors' conclusion. For example, the transcriptional function of XAP5 and XAP5L requires more evidence. In addition, this reviewer wonders about the conserved XAP5 function of ciliary/flagellar gene transcription in mammals - the gene is ubiquitously expressed despite its functional importance in flagellar assembly in Chlamydomonas. Thus, this reviewer thinks authors are required to show more direct evidence to clearly support their conclusion with more descriptions of its role in ciliary/flagellar assembly.
-
-
-