Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization.

Fabio M D’Orazio,Piotr J Balwierz,Bradley Cairns,Ferenc Müller,Ada Jimenez González,Lucy Wheatley,Yixuan Guo,Yavor Hadzhiev,Aleksandra Jasiulewicz,Boris Lenhard,Benjamín Hernández-Rodríguez,Juan M Vaquerizas

doi:10.1016/j.devcel.2021.02.007

Abstract

SummaryIn many animal models, primordial germ cell (PGC) development depends on maternally deposited germ plasm, which prevents somatic cell fate. Here, we show that PGCs respond to regulatory information from the germ plasm in two distinct phases using two distinct mechanisms in zebrafish. We demonstrate that PGCs commence zygotic genome activation together with the somatic blastocysts with no demonstrable differences in transcriptional and chromatin opening. Unexpectedly, both PGC and somatic blastocysts activate germ-cell-specific genes, which are only stabilized in PGCs by cytoplasmic germ plasm determinants. Disaggregated perinuclear relocalization of germ plasm during PGC migration is regulated by the germ plasm determinant Tdrd7 and is coupled to dramatic divergence between PGC and somatic transcriptomes. This transcriptional divergence relies on PGC-specific cis-regulatory elements characterized by promoter-proximal distribution. We show that Tdrd7-dependent reconfiguration of chromatin accessibility is required for elaboration of PGC fate but not for PGC migration.

Highlights

The germline ensures that parental genetic information is passed from one generation to the
Germ plasm factors have been associated with block or delay of zygotic genome activation (ZGA) of the hosting cell resulting in somatic fate escape
We focused on the first day of zebrafish embryogenesis, when primordial germ cell (PGC) form and migrate to the genital ridge (Figure 1A)

Summary

Introduction

The germline ensures that parental genetic information is passed from one generation to the next. The function of the germ plasm is to prevent somatic lineage differentiation of the host cells by at least two mechanisms Both vertebrates and invertebrates require germ plasm factors to regulate maternal RNA stability and translation (Charlesworth et al, 2006; Iguchi et al, 2006; Nakamura et al, 2004; Siddall et al, 2006; Krishnakumar et al, 2018; Wilhelm et al, 2003) that are cleared in the rest of the embryo as shown in zebrafish (Giraldez et al, 2006; Mishima et al, 2006). In C. elegans and D. melanogaster, the germ plasm proteins PIE-1 and Pgc delay ZGA, allowing the disengagement between the germ and the somatic lines (Batchelder et al, 1999; Mello et al, 1996; Strome and Updike, 2015)

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