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Title: Activation of the PAR polarity system in the C. elegans embryo
Author: Reich, Jacob Dietrich
ISNI:       0000 0004 7965 0363
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Most cell types exhibit some form of asymmetry, often termed polarity, creating distinct cell ends with specialised functions. One highly conserved mechanism for initially differentiating cell ends involves proteins of the PAR polarity network, which self-organise into opposing domains on the cortex of cells, generating an initial asymmetry which can act as a landmark for further asymmetries. For proper development and tissue homeostasis of multicellular organisms, polarity must be controlled in time, as many cell types undergo alternating periods of being polarised, and not being polarised. However, how the underlying PAR networks are temporally regulated, in terms of being able to respond to symmetry-breaking cues and polarise, is not well understood. The one-cell embryo of the model organism C. elegans is initially unpolarised, but polarises upon completion of maternal meiosis. This project has identified that the PAR network is initially inactive in immature oocytes, due to members of the anterior PAR complex being unable to associate with the cortex at this time. Oocyte maturation - independent of fertilisation or meiosis completion - was identified as the key process in activating the PAR network, by allowing anterior PARs to localise to the cortex, and localising posterior PARs to the cytoplasm. This renders the network capable of polarising the cortex in response to symmetry-breaking cues. Furthermore, anterior PAR cortical localisation is negatively regulated by the cell cycle regulators AuroraA and Polo-like kinase in oocytes, thus linking the activation of the PAR network to cell cycle progression, thereby enabling the proper coordination of PAR network activation and cue maturation, ensuring singularity of PAR domain formation.
Supervisor: Goehring, N. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available