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Title: BMP signalling via Id proteins in mesoderm progenitor cell differentiation
Author: Pegg, Amy Katrina
ISNI:       0000 0004 8497 7539
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2019
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Historically the three germ layer of the body: endoderm, ectoderm, and mesoderm, were considered to diverge early in development with the derivatives of each to progress along differentiation routes independent of one another. However, it is now known that neuromesodermal progenitors (NMPs) are present during axial elongation, after the basic formation of the three germ layers during gastrulation. These bipotent cells generate neurectodermal tissue in the form of the neural tube, giving rise to the central nervous system, and mesoderm in the formation of somites. NMPs are located within the anterior of the primitive streak, in the node streak border and the adjacent caudal lateral epiblast in the E8.5 mouse embryo. As axial elongation continues they are found in the chordoneural hinge within the tailbud until E13.5. Another progenitor population, denoted lateral and paraxial mesoderm progenitors (LPMPs) are found within the posterior of the primitive streak and the adjacent caudal lateral epiblast at E8.5. This progenitor population contributes to lateral and ventral mesoderm during embryonic development. However, grafting into NMP containing regions of the embryo has shown that these progenitors retain the ability to contribute to the paraxial mesoderm when in the appropriate environment. As the embryo begins elongation, Id transcripts can be detected within LPMP containing regions and are largely excluded from the regions that contain NMPs. The expression data generated here combined with previously published work identifies BMP signalling via Id factors as a candidate system for regulating mesoderm specification from progenitor populations within the primitive streak. As such, the work presented here utilises a combination of embryology and cell culture to examine the effects of BMP signalling via Id1 on the differentiation of progenitor populations within the primitive streak. Grafting data generated here indicates that NMPs possess plasticity in mesodermal differentiation, as with LPMPs. NMP regions were grafted into LPMP containing regions of the embryo and contributed well. An in vitro system was created to model the differentiation of NMPs into paraxial mesoderm and neurectoderm. Inducing BMP activity within this system inhibited differentiation into neurectodermal and paraxial mesoderm lineages, and instead led to the upregulation of markers of lateral and ventral mesoderm. As expected, treatment with BMP in this context also induced Id1 expression suggesting that the effects of BMP were being mediated via Id1. Specific induction of Id1 during NMP differentiation in vitro mimicked the effects of BMP treatment. The work described here extends expression data for the Id family in post implantation mouse development and presents a new cell based differentiation model. Utilising this system demonstrates that BMP signalling via Id1 can inhibit NMP differentiation into neurectoderm and paraxial mesoderm instead promoting differentiation into lateral and ventral mesoderm.
Supervisor: Lowell, Sally ; Wilson, Val Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Id protein ; Id1 ; BMP ; NMPs ; embryonic development ; mesoderm ; neural