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Co-option of the piRNA pathway to regulate neural crest specification

Galton, Riley and Fejes-Tóth, Katalin and Bronner, Marianne E. (2022) Co-option of the piRNA pathway to regulate neural crest specification. Science Advances, 8 (32). Art. No. abn1441. ISSN 2375-2548. doi:10.1126/sciadv.abn1441.

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Across Metazoa, Piwi proteins play a critical role in protecting the germline genome through piRNA-mediated repression of transposable elements. In vertebrates, activity of Piwi proteins and the piRNA pathway was thought to be gonad specific. Our results reveal the expression of Piwil1 in a vertebrate somatic cell type, the neural crest. Piwil1 is expressed at low levels throughout the chicken neural tube, peaking in neural crest cells just before the specification event that enables epithelial-to-mesenchymal transition (EMT) and migration into the periphery. Loss of Piwil1 impedes neural crest specification and emigration. Small RNA sequencing reveals somatic piRNAs with sequence signatures of an active ping-pong loop. RNA-seq and functional experiments identify the transposon-derived gene ERNI as Piwil1’s target in the neural crest. ERNI, in turn, suppresses Sox2 to precisely control the timing of neural crest specification and EMT. Our data provide mechanistic insight into a novel function of the piRNA pathway as a regulator of somatic development in a vertebrate species.

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Galton, Riley0000-0001-6777-2177
Fejes-Tóth, Katalin0000-0001-6558-2636
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Received: 5 November 2021. Accepted: 24 June 2022. We thank members of the M.E.B., K.F.-T., and Aravin laboratories for helpful discussions. We thank M. Ninova for advice on RNA-seq analysis and for making the ping-pong script available for our use. We also thank M. Piacentino for advice with imaging analysis and providing Fiji macros for our use. We thank Q. 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 I. Antoshechkin for advice on data analysis and ensuring that our small RNA libraries were sequenced during the COVID-19 lockdown. This work is supported by NIH grants R01GM110217 to K.F.-T. and R35NS111564 to M.E.B. R.G. was supported by the NSF’s GRFP fellowship. Author contributions: Conceptualization: R.G., K.F.-T., and M.E.B. Investigation: R.G. Formal analysis: R.G. Visualization: R.G. Funding acquisition: R.G., K.F.-T., and M.E.B. Supervision: K.F.-T. and M.E.B. Writing (original draft): R.G. Writing (review and editing): R.G., K.F.-T., and M.E.B. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. All raw sequencing data generated for this publication are available through Gene Expression Omnibus. Neural fold RNA-seq data (Fig. 3 and figs. S2 and S4) are available with accession number GSE171615 and small RNA-seq data (Figs. 1 and 3and fig. S3) with GSE171616. Previously published specified neural crest datasets (fig. S2) are available from NCBI BioProject no. PRJNA497902. All scripts used in this publication are included in table S2. The authors declare that they have no competing interests.
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
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NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:32
Record Number:CaltechAUTHORS:20220811-456719000
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Official Citation:Galton R, Fejes-Toth K, Bronner ME. Co-option of the piRNA pathway to regulate neural crest specification. Sci Adv. 2022;8(32):eabn1441. doi:10.1126/sciadv.abn1441
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:116235
Deposited By: George Porter
Deposited On:12 Aug 2022 02:06
Last Modified:12 Aug 2022 02:06

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