Preprint: Please note that this article has not completed peer review.
Research article

Role of PRY-1/Axin in heterochronic miRNA-mediated seam cell development

Avijit Mallick, Ayush Ranawade, Bhagwati P Gupta
DOI: 10.21203/rs.2.10111/v1

Abstract

Background

Caenorhabditis elegans seam cells serve as a good model to understand how genes and signaling pathways interact to control asymmetric cell fates. The stage-specific pattern of seam cell division is coordinated by a genetic network that includes WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, as well as heterochronic microRNA (miRNAs) and their downstream targets. Mutations in pry-1, a negative regulator of WNT signaling that belongs to the Axin family, were shown to cause seam cell defects; however, the mechanism of PRY-1 action and its interactions with miRNAs remain unclear.

Results

We found that pry-1 mutants in C. elegans exhibit seam cell, cuticle, and alae defects. To examine this further, a miRNA transcriptome analysis was carried out, which showed that let-7 (miR-48, miR-84, miR-241) and lin-4 (lin-4, miR-237) family members were upregulated in the absence of pry-1 function. Similar phenotypes and patterns of miRNA overexpression were also observed in C. briggsae pry-1 mutants, a species that is closely related to C. elegans. RNA interference-mediated silencing of wrm-1 and lit-1 in the C. elegans pry-1 mutants rescued the seam cell defect, whereas pop-1 silencing enhanced the phenotype, suggesting that all three proteins are likely important for PRY-1 function in seam cells. We also found that these miRNAs were overexpressed in pop-1 hypomorphic animals, suggesting that PRY-1 may be required for POP-1-mediated miRNA suppression. Analysis of the let-7 and lin-4-family heterochronic targets lin-28 and hbl-1 showed that both genes were significantly downregulated in pry-1 mutants, and furthermore, lin-28 silencing reduced the number of seam cells in mutant animals.

Conclusions

Our results show that PRY-1 plays a conserved role to maintain normal expression of heterochronic miRNAs in nematodes. Furthermore, we demonstrated that PRY-1 acts upstream of the WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, and miRNA target genes in seam cell development.

Keywords
C. elegans, C. briggsae, pry-1, Axin, WNT asymmetry pathway, seam cell, miRNA, heterochronic development

Figures

Background

Results

Discussion

Conclusions

Methods

List of abbreviations

Declarations

References

Supplementary Files

STATUS: In Review

Comments: 0
PDF Downloads: 4
HTML Views: 27

Integrity Check:

Peer Review Timeline

Version 1

Posted 19 Jun, 2019

  • No community comments so far
  • Editorial decision: Accept

    On 28 Jun, 2019

  • Review #2 received

    Received 25 Jun, 2019

  • Reviewer #2 agreed

    On 07 Jun, 2019

  • Review #1 received

    Received 06 Jun, 2019

  • Reviewer #1 agreed

    On 05 Jun, 2019

  • Submission checks complete

    On 03 Jun, 2019

  • 3 reviewer(s) invited

    Invitations sent on 03 Jun, 2019

  • Editor assigned

    On 31 May, 2019

  • Editor invited

    On 31 May, 2019

  • First submitted

    On 28 May, 2019

More from BMC Developmental Biology

Comments (0)

Comments can take the form of short reviews, notes or questions to the author. Comments will be posted immediately, but removed and moderated if flagged.

Learn more about our company.

Preprint: Please note that this article has not completed peer review.
Research article

Role of PRY-1/Axin in heterochronic miRNA-mediated seam cell development

Avijit Mallick, Ayush Ranawade, Bhagwati P Gupta

STATUS: In Review

Comments: 0
PDF Downloads: 4
HTML Views: 27

Integrity Check:

  • Article

  • Peer Review Timeline

  • Related Articles

  • Comments

Abstract

Background

Caenorhabditis elegans seam cells serve as a good model to understand how genes and signaling pathways interact to control asymmetric cell fates. The stage-specific pattern of seam cell division is coordinated by a genetic network that includes WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, as well as heterochronic microRNA (miRNAs) and their downstream targets. Mutations in pry-1, a negative regulator of WNT signaling that belongs to the Axin family, were shown to cause seam cell defects; however, the mechanism of PRY-1 action and its interactions with miRNAs remain unclear.

Results

We found that pry-1 mutants in C. elegans exhibit seam cell, cuticle, and alae defects. To examine this further, a miRNA transcriptome analysis was carried out, which showed that let-7 (miR-48, miR-84, miR-241) and lin-4 (lin-4, miR-237) family members were upregulated in the absence of pry-1 function. Similar phenotypes and patterns of miRNA overexpression were also observed in C. briggsae pry-1 mutants, a species that is closely related to C. elegans. RNA interference-mediated silencing of wrm-1 and lit-1 in the C. elegans pry-1 mutants rescued the seam cell defect, whereas pop-1 silencing enhanced the phenotype, suggesting that all three proteins are likely important for PRY-1 function in seam cells. We also found that these miRNAs were overexpressed in pop-1 hypomorphic animals, suggesting that PRY-1 may be required for POP-1-mediated miRNA suppression. Analysis of the let-7 and lin-4-family heterochronic targets lin-28 and hbl-1 showed that both genes were significantly downregulated in pry-1 mutants, and furthermore, lin-28 silencing reduced the number of seam cells in mutant animals.

Conclusions

Our results show that PRY-1 plays a conserved role to maintain normal expression of heterochronic miRNAs in nematodes. Furthermore, we demonstrated that PRY-1 acts upstream of the WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, and miRNA target genes in seam cell development.

Figures

Background

Results

Discussion

Conclusions

Methods

List of abbreviations

Declarations

References

Learn more about our company.