Abstract

ABSTRACTThe unique developmental characteristics of chicken primordial germ cells (PGCs) enable them to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits their application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the mechanism underlying chicken PGC formation has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of Lin28A by inducing β-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhancing H3K4me2 methylation in this region. Lin28A promotes PGC formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt–Lin28A–Blimp1–Wnt that ensures PGC formation. In summary, our data provide new insight into the development of PGCs in chickens.

Highlights

  • Primordial germ cells (PGCs) are the progenitors of sperm and ovum, which are responsible for the transmission of genetic information between germ lines (Liu et al, 2018; Nakamura, 2017)

  • We found that BMP4 and Wnt signaling are significantly upregulated during chicken PGC formation via RNA sequencing (RNA-seq) of chicken embryonic stem cells (ESCs) and PGCs (Zhang et al, 2015)

  • Gene ontology (GO) analysis showed that 2516 differentially expressed genes (DEGs) were enriched in development-related terms (Fig. S1A,B and Table S1), 20 genes of which were significantly enriched in the Wnt signaling pathway (P=0.0023) (Fig. 1C; Table S2)

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Summary

Introduction

Primordial germ cells (PGCs) are the progenitors of sperm and ovum, which are responsible for the transmission of genetic information between germ lines (Liu et al, 2018; Nakamura, 2017). Chicken PGCs have the characteristic of migrating to the genital ridge via the blood, which enables their wide application in recovery of endangered bird species, gene editing and the generation of transgenic birds (Lu et al, 2014; Ono and Machida, 1999; Zhao and Kuwana, 2003). Studying the molecular mechanisms underlying chicken PGC formation could facilitate the application of PGCs. The molecular mechanisms underlying PGC formation in mammals have been well studied; such research in chicken PGCs has been limited. Because of species differences, it is not clear whether the mechanisms of PGC formation in mammals can be applied to chickens

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