Comparative Analysis of Primordial Germ Cell Specification: “What Is a Germline and How Do I Get One?”

Foster, Stephany

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Year:: 2022
Contributor:: Foster, Stephany (creator); Wessel, Gary (Advisor); Behringer, Richard (Reader); Freiman, Richard (Reader); Wharton, Kristi (Reader); Neretti, Nicola (Reader); Brown University. Department of Molecular Biology, Cell Biology and Biochemistry (sponsor)
Genre:: theses
Subject:: Germ cells
Extent:: xiii, 346 p.

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Abstract:: Specification of the germline, the cells which give rise to eggs and sperm, is essential for sexually reproducing organisms. The mechanism by which animals specify their germline falls into two categories: inherited or inductive. Echinoderms appear to use diverse mechanisms in germline formation. The sea urchin (Strongylocentrotus purpuratus) specifies its germline by inheritance of stored maternal molecules, representative of the inherited mechanism. We recently performed a scRNA-seq analysis of early sea urchin development and identified the transcript profile of the germ cell precursors. The inductive mechanism, used by mammals, relies on cell signaling interactions to direct a subset of embryonic cells to a germ cell fate. Implantation of the mammalian embryo precludes direct, detailed examination of this mechanism in mammals, but previous work suggested that sea star (Patiria miniata) embryos, which develop in simple media and are markedly transparent, also use inductive mechanisms to specify their germline. The germ cell factors Nanos and Vasa become restricted in a subset of cells within the posterior enterocoel (PE), the presumptive germline. Nodal signaling was observed to negatively regulate Vasa and Nanos mRNAs to restrict their expression to the PE. Despite the recurrence of the inductive germline mechanism across metazoa, the full network of signals that directs this process remains poorly understood. We learned that Wnt and Delta/Notch signaling enhances Nanos and Vasa expression, whereas a test of dependency in cell interactions reveals that Nanos and Vasa are regulated distinctly. Single-cell analysis of early sea star embryos reveals co-expression of germ cell genes with mesodermal markers suggesting a mesodermal precursor state similar to what has been seen in other species employing inductive germ cell specification. This work provides insight into the ancestral mechanism of germ cell specification and its evolution across the tree of life. Additionally, the results from this work contrast the results of PGC specification in the sea urchin and enables deeper comparative mechanistic studies in tractable in vivo models.
Notes:: Thesis (Ph. D.)--Brown University, 2022

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Citation

Foster, Stephany, "Comparative Analysis of Primordial Germ Cell Specification: “What Is a Germline and How Do I Get One?”" (2022). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:n3sr2j7p/

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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