1. Developmental Biology

Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual

  1. Tianyu Zhu
  2. Yuxin Zhang
  3. Xunlun Sheng
  4. Xiangzheng Zhang
  5. Yu Chen
  6. Hongjing Zhu
  7. Yueshuai Guo
  8. Yaling Qi
  9. Yichen Zhao
  10. Qi Zhou
  11. Xue Chen  Is a corresponding author
  12. Xuejiang Guo  Is a corresponding author
  13. Chen Zhao  Is a corresponding author
  1. Nanjing Medical University, China
  2. Fudan University, China
  3. Gansu Aier Ophthalmiology and Optometry Hospital, China
  4. The First Affiliated Hospital of Nanjing Medical University, China
https://doi.org/10.7554/eLife.76157
Share this article
Cite this article
  1. Tianyu Zhu
  2. Yuxin Zhang
  3. Xunlun Sheng
  4. Xiangzheng Zhang
  5. Yu Chen
  6. Hongjing Zhu
  7. Yueshuai Guo
  8. Yaling Qi
  9. Yichen Zhao
  10. Qi Zhou
  11. Xue Chen
  12. Xuejiang Guo
  13. Chen Zhao
(2023)
Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual
eLife 12:e76157.
https://doi.org/10.7554/eLife.76157
  2. Download BibTeX
  3. Download .RIS

Abstract

Cone rod dystrophy (CRD) is a genetically inherited retinal disease that can be associated with male infertility, while the specific genetic mechanisms are not well known. Here we report CEP78 as a causative gene of a particular syndrome including CRD and male infertility with multiple morphological abnormalities of sperm flagella (MMAF) both in human and mouse. Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced electroretinogram amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures. Cep78 deletion also caused male infertility and MMAF, with disordered '9 + 2' structure and triplet microtubules in sperm flagella. Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. Furthermore, CEP78 regulated the interaction, stability, and centriolar localization of its interacting protein. Insufficiency of CEP78 or its interacting protein causes abnormal centriole elongation and cilia shortening. Absence of CEP78 protein in human caused similar phenotypes in vision and MMAF as Cep78-/- mice. Collectively, our study supports the important roles of CEP78 defects in centriole and ciliary dysfunctions and molecular pathogenesis of such multi-system syndrome.

Data availability

All H&E, PAS, immunofluorescence, TEM, SEM, uncropped gels and blots, and statistical data are available at corresponding source data files. All mass spectrometry data are available at Dryad deposit:Data of IP-MS was submitted to Dryad (Zhu, Tianyu et al. (2021), Anti-Cep78 immunoprecipitation (IP) coupled with quantitative MS (IP-MS) on testicular lysates of Cep78+/- and Cep78-/- mice, Dryad, Dataset).Data of quantitative MS on elongating spermatids lysates was submitted to Dryad (Dataset, Zhu, Tianyu et al. (2021), Quantitative mass spectrometry (MS) on elongating spermatids lysates of Cep78+/- and Cep78-/- mice, Dryad, Dataset).

The following data sets were generated

Article and author information

Author details

  1. Tianyu Zhu

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Yuxin Zhang

    Department of Ophthalmology and Vision Science, Fudan University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Xunlun Sheng

    Gansu Aier Ophthalmiology and Optometry Hospital, Lanzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Xiangzheng Zhang

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Yu Chen

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Hongjing Zhu

    Department of Ophthalmology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Yueshuai Guo

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Yaling Qi

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2940-4733

  9. Yichen Zhao

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Qi Zhou

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Xue Chen

    Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    For correspondence
    drcx1990@vip.163.com
    Competing interests
    The authors declare that no competing interests exist.

  12. Xuejiang Guo

    Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    For correspondence
    guo_xuejiang@njmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0475-5705

  13. Chen Zhao

    Department of Ophthalmology and Vision Science, Fudan University, Shanghai, China
    For correspondence
    dr_zhaochen@163.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1373-7637

Funding

National Key Research and Development Program of China (2021YFC2700200)

  • Xuejiang Guo

Shanghai Outstanding Academic Leaders (2017BR013)

  • Chen Zhao

Six Talent Peaks Project in Jiangsu Province (YY-019)

  • Xuejiang Guo

Basic Research Program of Jiangsu Province (BK20220316)

  • Tianyu Zhu

Scientific Research Project of Gusu School of Nanjing Medical University (GSBSHKY20213)

  • Tianyu Zhu

National Natural Science Foundation of China (82020108006)

  • Chen Zhao

National Natural Science Foundation of China (81730025)

  • Chen Zhao

National Natural Science Foundation of China (81971439)

  • Xuejiang Guo

National Natural Science Foundation of China (81771641)

  • Xuejiang Guo

National Natural Science Foundation of China (82070974)

  • Xue Chen

National Natural Science Foundation of China (82060183)

  • Xunlun Sheng

National Natural Science Foundation of China (82201764)

  • Tianyu Zhu

China Postdoctoral Science Foundation (2022M711676)

  • Tianyu Zhu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mice were raised in a specific-pathogen-free animal facility accredited by Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) in Model Animal Research Center, Nanjing University, China. The facility provided ultraviolet sterilization, a 12-hour light/dark cycle, ad libitum access to water, and standard mouse chow diet. Mice experiments were performed in accordance with approval of the Institutional Animal Care and Use Committee of Nanjing Medical University (IACUC-1707017-8) and with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.

Human subjects: Our study, conformed to the Declaration of Helsinki, was prospectively reviewed, and approved by the ethics committee of People's Hospital of Ningxia Hui Autonomous Region ([2016] Ethic Review [Scientific Research] NO. 018) and Nanjing Medical University (NMU Ethic Review NO. (2019) 916). Signed informed consents were obtained from all individuals in the study.

Copyright

© 2023, Zhu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,222
    views
  • 261
    downloads
  • 7
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tianyu Zhu
  2. Yuxin Zhang
  3. Xunlun Sheng
  4. Xiangzheng Zhang
  5. Yu Chen
  6. Hongjing Zhu
  7. Yueshuai Guo
  8. Yaling Qi
  9. Yichen Zhao
  10. Qi Zhou
  11. Xue Chen
  12. Xuejiang Guo
  13. Chen Zhao
(2023)
Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual
eLife 12:e76157.
https://doi.org/10.7554/eLife.76157

Share this article

https://doi.org/10.7554/eLife.76157

Categories and tags

Research organisms

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Single-cell RNA sequencing of the holothurian regenerating intestine reveals the pluripotency of the coelomic epithelium

    Joshua G Medina-Feliciano, Griselle Valentín-Tirado ... José E Garcia-Arraras
    Research Article

    In holothurians, the regenerative process following evisceration involves the development of a ‘rudiment’ or ‘anlage’ at the injured end of the mesentery. This regenerating anlage plays a pivotal role in the formation of a new intestine. Despite its significance, our understanding of the molecular characteristics inherent to the constituent cells of this structure has remained limited. To address this gap, we employed state-of-the-art scRNA-seq and hybridization chain reaction fluorescent in situ hybridization analyses to discern the distinct cellular populations associated with the regeneration anlage. Through this approach, we successfully identified 13 distinct cell clusters. Among these, two clusters exhibit characteristics consistent with putative mesenchymal cells, while another four show features akin to coelomocyte cell populations. The remaining seven cell clusters collectively form a large group encompassing the coelomic epithelium of the regenerating anlage and mesentery. Within this large group of clusters, we recognized previously documented cell populations such as muscle precursors, neuroepithelial cells, and actively proliferating cells. Strikingly, our analysis provides data for identifying at least four other cellular populations that we define as the precursor cells of the growing anlage. Consequently, our findings strengthen the hypothesis that the coelomic epithelium of the anlage is a pluripotent tissue that gives rise to diverse cell types of the regenerating intestinal organ. Moreover, our results provide the initial view into the transcriptomic analysis of cell populations responsible for the amazing regenerative capabilities of echinoderms.

    1. Cell Biology
    2. Developmental Biology

    Rediscovering the rete ovarii, a secreting auxiliary structure to the ovary

    Dilara N Anbarci, Jennifer McKey ... Blanche Capel
    Research Article

    The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the mouse ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow toward the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

    1. Cell Biology
    2. Developmental Biology

    Ovarian Biology: Revisiting the rete ovarii

    Yan Zhang, Hua Zhang
    Insight

    Long thought to have little relevance to ovarian physiology, the rete ovarii may have a role in follicular dynamics and reproductive health.