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A somatic piRNA pathway regulates epithelial-to-mesenchymal transition of chick neural crest cells

Galton, Riley and Fejes-Tóth, Katalin and Bronner, Marianne E. (2021) A somatic piRNA pathway regulates epithelial-to-mesenchymal transition of chick neural crest cells. . (Unpublished)

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In the metazoan germline, Piwi proteins play an essential regulatory role in maintenance of stemness and self-renewal by piRNA-mediated repression of transposable elements. To date, the activity of Piwi proteins and the piRNA pathway in vertebrates was believed to be confined to the gonads. Our results reveal expression of Piwil1 in a vertebrate somatic cell type, the neural crest — a migratory embryonic stem cell population. We show that Piwil1 is expressed at low levels throughout chick neural crest development, peaking just before neural crest cells undergo an epithelial-to-mesenchymal transition to leave the neural tube and migrate into the periphery. Importantly, loss of Piwil1 impedes neural crest emigration. Small RNA sequencing reveals somatic piRNAs with sequence signatures of an active ping pong loop. Coupled with Piwil1 knockout RNA-seq, our data suggest that Piwil1 regulates expression of the transposon derived gene ERNI in the chick dorsal neural tube, which in turn suppresses Sox2 expression to precisely control the timing of neural crest specification and emigration. Our work provides mechanistic insight into a novel function of the piRNA pathway as a regulator of somatic development in vertebrates.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Galton, Riley0000-0001-6777-2177
Fejes-Tóth, Katalin0000-0001-6558-2636
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted April 30, 2021. We thank members of the Bronner, Fejes Toth and Aravin labs for helpful discussions. We thank Maria Ninova for advice on RNA-seq analysis, as well as for making the pingpong script available for our use. We also thank Michael Piacentino for advice with imaging analysis and providing FIJI macros for our use. We thank Qing Tang for providing us with the mini CMV promoter. We acknowledge the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory for library prep and sequencing of our CRISPR RNA-seq experiment, and in particular thank Igor Antoshechkin for advice on data analysis, as well as ensuring that our small RNA libraries got sequenced during the COVID-19 pandemic. This work is supported by NIH grants R01GM110217 to KFT and R35NS111564 to MB. RG was supported by the NSF GRFP fellowship. Author contributions: RG, MB and KFT designed experiments; RG conducted all experiments and data analysis; RG, MB and KFT wrote the manuscript. The authors declare no competing financial interests. Data availability statement: All raw sequencing data generated for this publication is available upon reasonable request from the corresponding authors, and will available through Gene Expression Omnibus upon publication. Previously published specified neural crest datasets are available from NCBI BioProject# PRJNA497902.
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NSF Graduate Research FellowshipUNSPECIFIED
Record Number:CaltechAUTHORS:20210504-121027939
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Official Citation:A somatic piRNA pathway regulates epithelial-to-mesenchymal transition of chick neural crest cells. Riley Galton, Katalin Fejes-Toth, Marianne E. Bronner. bioRxiv 2021.04.30.442165; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108963
Deposited By: Tony Diaz
Deposited On:05 May 2021 17:36
Last Modified:16 Nov 2021 19:33

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