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Title: Mechanisms of germ cell formation during zebrafish embryogenesis
Author: D'Orazio, Fabio Marco
ISNI:       0000 0004 8499 8209
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2019
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In metazoans, the germ fate is acquired during embryogenesis either via oocyte-inherited cytoplasmic aggregates or via chemical induction from the surrounding embryonic cells. Most of the model organisms, including Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis and Danio rerio, rely on maternal determinants necessary to generate the germ line of the offspring. Although it has been largely established that germ determinants are required for the formation of germ cells, the specific molecular mechanisms driving the onset of the germ line are still unclear. Germ granules have been implicated in transcriptional inhibition contributing to skipping somatic differentiation. Also, epigenetic reprogramming of the embryonic germ line has been shown in several model organisms. However, little is known about the role of the germ plasm in transcription and epigenetics. Here, we show that the germ plasm and the epigenetic landscape of zebrafish primordial germ cells (PGCs) are tightly linked. The early germ line shows similar transcriptional timing, transcriptomic and chromatin profiles with the rest of the embryo and the germ fate is gradually acquired during the first day of development. A PGC-like chromatin profile is acquired while germ plasm re-localises within the cells and PGCs and somatic cells undergo significant epigenetic and transcriptional divergence. By performing time series of chromatin and transcript profiles in the PGCs, we could identify candidate PGC-specific cis-regulatory elements and transcripts. We detect both hypermethylation and chromatin compaction around putative developmental enhancers indicating that the germ fate is acquired avoiding lineage differentiation. Finally, to link epigenetic dynamics to germ plasm behaviour, we inhibited the translation of Tudor Domain 7 (Tdrd7), a germ-plasm-localised protein involved in structural organisation of the germ granules. The mutant embryos reprogram the PGC-specific chromatin state and resemble the somatic cells, suggesting that the germ plasm is primarily responsible for epigenetically preserving the pluripotent state of the PGCs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)