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Co-Option of the piRNA Pathway to Regulate Neural Crest Specification


Galton, Riley (2023) Co-Option of the piRNA Pathway to Regulate Neural Crest Specification. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/9rvr-rr55.


The piRNA pathway has persisted throughout evolution as an essential regulatory pathway to protect genomic integrity in the metazoan germline. It achieves this through the repression of transposable elements, or “selfish genes,” which would otherwise jump throughout the genome unchecked, causing genomic instability and infertility. While transposable elements are generally deleterious in nature, their persistence in our genome remains an important driver of evolution, both as an agent of mutation and source of raw genetic material. Thus, a delicate balance must be struck to both maintain genomic integrity for the next generation but still enable enough mutation to allow for adaptation. The arms race between the ever-adapting piRNA pathway and its transposon targets provides this balance, and for a long time the piRNA pathway was considered to be germline specific, since that is where both transposon and piRNA pathway activity is highest. It has since become clear that the piRNA pathway is also active in somatic tissue of several invertebrate species, and may even target host genes in some. Whether the piRNA pathway plays a role outside of the germline in vertebrates, however, has remained elusive.

In this thesis, we demonstrate that the piRNA pathway is active in a vertebrate somatic cell type, the chick neural crest, where it has been co-opted into the gene regulatory network to repress the transposon-derived gene, ERNI. ERNI, in turn, supresses Sox2 when piRNA pathway protein Piwil1 is downregulated upon neural crest specification. Thus, the piRNA pathway functions to maintain Sox2 expression in the neural plate border stem cell niche, protecting its proliferative abilities and setting the timing of neural crest specification. We also provide preliminary evidence that the neural crest piRNA pathway might be conserved in other vertebrate species, and that two highly conserved transcription factors regulate its expression in the chick neural crest. Our work provides mechanistic insight into a novel function of the piRNA pathway as a regulator of somatic development in vertebrates, and raises the possibility that this ancient pathway may play a more significant role in evolution and transposon co-option by host genomes than previously thought.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:piRNA, Piwi, neural crest, embryonic development
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Developmental Biology
Awards:Society for Developmental Biology Best Student Poster Competition, honorable mention 2021; NSF Graduate Research Fellowship, 2017; NSF Graduate Research Fellowship Program, honorable mention, 2016
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Bronner, Marianne E. (co-advisor)
  • Fejes Tóth, Katalin (co-advisor)
Thesis Committee:
  • Rothenberg, Ellen V. (chair)
  • Bronner, Marianne E.
  • Fejes-Tóth, Katalin
  • Aravin, Alexei A.
  • Zernicka-Goetz, Magdalena
Defense Date:22 September 2022
Funding AgencyGrant Number
Record Number:CaltechTHESIS:01232023-192745187
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Ch. 2
Galton, Riley0000-0001-6777-2177
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15091
Deposited By: Riley Galton
Deposited On:24 Feb 2023 00:04
Last Modified:04 Jun 2024 23:08

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