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  4. Dissecting the mechanisms of centriole stability in Caenorhabditis elegans: Focus on SAS-1
 
doctoral thesis

Dissecting the mechanisms of centriole stability in Caenorhabditis elegans: Focus on SAS-1

Jha, Keshav  
2025

Centrioles are evolutionarily conserved microtubule-based organelles essential for cell division, ciliogenesis, and cell polarity. While centrioles are critical for many cellular processes, their selective elimination is crucial during specific developmental stages, particularly in oogenesis and embryogenesis. Throughout metazoans, oocytes eliminate their centrioles while sperm usually contributes two centrioles during fertilization, ensuring proper centriole numbers in the zygote. However, the molecular mechanisms governing these differential fates of centrioles in gametes remain poorly understood. In this doctoral work, I investigated the factors controlling centriole stability using the nematode C. elegans as the model organism.
The protein SAS-1, a worm homolog of human C2CD3, was identified as being required for maintaining the stability of sperm-contributed centrioles post-fertilization. We investigated whether SAS-1 might be part of a broader mechanism ensuring centriole stability during early meiotic prophase in the female germline and in specific cell lineages retaining centrioles during embryogenesis. Using a combination of genetic tools and microscopy, we demonstrated that SAS-1 is a component of the centriolar central tube. We found that SAS-1 depletion results in premature centriole loss during oogenesis and compromises centriole structure in sperm. Although SAS-1 is necessary for centriole stability, artificial tethering of excess SAS-1 to centriolar proteins proved insufficient to prevent centriole elimination. We also characterized SSNA-1, a potential SAS-1-binding protein that colocalizes at the central tube. Our findings revealed that while SAS-1 is required for SSNA-1 recruitment to centrioles, SSNA-1 reciprocally stabilizes SAS-1 at centrioles. Notably, we identified SAS-1 as the first known centriolar protein to localize at the transition zone of sensory cilia, with its loss resulting in subtle ciliary defects.
Additionally, we explored the potential role of centrioles in non-proliferative cells during larval development. Through targeted SAS-4 depletion during late embryogenesis, we achieved artificial centriole elimination. Interestingly, while centriole loss did not prevent the transdifferentiation of Y cells to PDA neurons, it did cause a delay in this process.
Collectively, this work provides insights into the molecular mechanisms of centriole stability and elimination during development. Our findings establish SAS-1 as a key regulator of centriole maintenance across different tissues in C. elegans.

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Type
doctoral thesis
DOI
10.5075/epfl-thesis-11045
Author(s)
Jha, Keshav  
Advisors
Gönczy, Pierre  
Jury

Prof. Daniel Constam (président) ; Prof. Pierre Gönczy (directeur de thèse) ; Prof. Andrew Oates, Prof. Peter Meister, Prof. Mónica  Bettencourt Dias (rapporteurs)

Date Issued

2025

Publisher

EPFL

Publisher place

Lausanne

Public defense year

2025-02-20

Thesis number

11045

Total of pages

124

Subjects

Centrioles

•

C. elegans

•

SAS-1

•

centriole elimination

•

centriole stability

•

U-Ex-STED

•

microscopy

EPFL units
UPGON  
Faculty
SV  
School
ISREC  
Doctoral School
EDMS  
Available on Infoscience
February 12, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/246892
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