Vong, Yin Ho (2019) Regulation of zebrafish embryogenesis by the RNAbinding protein Igf2bp3. PhD thesis, University of Warwick.

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Abstract

During development, establishment of the germline is an early event that is essential for ensuring the future embryo has reproductive capability. Precursors of the germline originate as primordial germ cells, which are specified far from their destination where the gonads will develop, and these cells require cues to migrate, proliferate and sustain their fates.

In zebrafish, development of the germline is controlled by maternally contributed factors known as germplasm, a collection of RNA that is tightly regulated by proteins, forming ribonucleoprotein complexes, and cells receiving this material are fated to become the PGCs; and misregulation of the germplasm leads to defects in the germline.

In this study, we have examined the role of the igf2bp family of RNA-binding proteins, which are implicated in many functions in RNA metabolism, such as localisation, stability and translation, with disruption of these genes in vivo leading to developmental consequences in the soma. Using transgenic insertion alleles and Cas9 mutant alleles for igf2bp3, we characterised the role of igf2bp3 in zebrafish development.

Contrary to previous studies, maternal-zygotic igf2bp3 mutants did not show any overt defects in the soma, developing to adulthood with no apparent disabilities. However, maternal igf2bp3 mutants are developmentally delayed around blastula, exhibiting an expanded yolk syncytial layer, and otherwise continue developing with no further defects. Moreover, these maternal mutants also exhibit an aberrant germline, with PGCs displaying abnormal behaviour and are depleted in the gonadal ridge, leading to a skewed sex ratio.

These results point to a novel function for igf2bp genes in early development and germline formation, and future studies in uncovering the mechanism may show new insights for Igf2bp3 in regulating germplasm, by regulating the fates of directly bound transcripts, or as part of a ribonucleoprotein complex.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QL Zoology Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Zebra danio -- Embryology, RNA-protein interactions, Protein binding, Germ cells, Embryonic stem cells
Official Date:	September 2019
Dates:	Date Event September 2019 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Sampath, Karuna, 1967- ; Jones, Alexandra M.
Format of File:	pdf
Extent:	xii, 219 leaves : illustrations
Language:	eng

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