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

Area of Science:

• Developmental Biology
• Molecular Biology
• Genomics

Background:

• Piwi proteins and piRNA pathways are essential for germline genome integrity by repressing transposable elements across Metazoa.
• In vertebrates, Piwi protein and piRNA pathway activity was traditionally considered restricted to the gonads.

Purpose of the Study:

• To investigate the role of Piwi proteins beyond the germline, specifically in vertebrate somatic development.
• To explore the function of Piwil1 in neural crest cell specification, epithelial-to-mesenchymal transition (EMT), and migration.

Main Methods:

• Analysis of Piwil1 expression in chicken neural tube and neural crest cells.
• Small RNA sequencing to identify somatic piRNAs and their characteristics.
• RNA sequencing and functional experiments to identify Piwil1 targets and downstream effects.
• Investigating the impact of Piwil1 loss on neural crest specification and emigration.

Main Results:

• Piwil1 is expressed in a vertebrate somatic cell type, the neural crest, peaking before EMT and migration.
• Loss of Piwil1 function impairs neural crest specification and emigration.
• Somatic piRNAs indicative of an active ping-pong loop were detected.
• The transposon-derived gene ERNI was identified as a Piwil1 target in neural crest cells, suppressing Sox2 to regulate neural crest specification and EMT timing.

Conclusions:

• The piRNA pathway, through Piwil1, plays a novel role in regulating somatic development in vertebrates.
• Piwil1 acts via the ERNI-Sox2 axis to control the precise timing of neural crest specification and EMT.
• This study expands the known functions of Piwi proteins and the piRNA pathway to somatic cell regulation during vertebrate development.