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Title: Investigating the role of pal-1, the C. elegans caudal homologue, in the development of the stem-like seam cells
Author: Gilbert, Sophie Patricia Rose
ISNI:       0000 0004 6353 179X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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An organism's epithelium provides essential protection against mechanical stress and pathogenic infection, as well as specialised secretory and sensory functions. Intriguingly, at the end of the first larval moult in C. elegans, epidermal P cells, which until now have comprised the majority of the ventral epidermis, migrate and remodel, relinquishing their epidermal role before taking on neuroectoblast fate. This leaves a ventral 'hole' in the architecture of the C. elegans epidermis. This work describes how this hole is filled by a hitherto-overlooked ventral intercalation event that mirrors the well-described dorsal epidermal intercalation that takes place during embryogenesis and forms the dorsal hyp7 epidermal syncytium. Ventral intercalation involves polarised PAK-dependent cytoskeletal remodelling of anterior daughters of asymmetric (seam) stem cell divisions, prior to P cell migration, between the P cells. Conversely, the posterior seam-fated (self-renewing) daughters retain their lateral positions. This ensures the anterior daughters move ventrally to replace the P cells as they migrate into the ventral midline; thus, for the first time, the major syncytial epidermal organ, hyp7, on the ventral side of the animal is completed. Using this novel system, I have shown that patterning of adjacent epidermal tissues by pal-1/caudal, through expression driven by a putative Wnt-dependent intronic enhancer, determines the polarity of apical junction remodelling and thus polarity of migration during intercalation. Furthermore, the change of gene expression, structure and function of the P cells during this major epidermal remodelling event appears indicative of a transdifferentiation event. An enhancer/suppressor screen for pal-1 epidermal phenotypes during this newly described ventral intercalation has identified a novel role for netrin during posterior embryonic patterning. I have shown that this phenotype is dependent on an interaction with pal-1 of both netrin receptors, UNC-40 and UNC-5, as well as having identified an unc-40-independent role for unc-5 and pal-1 earlier in development. Conversely, I have also discovered a role for pal-1 in post-embryonic netrin-dependent motor neurone axon guidance. Given the high levels of conservation between members of the netrin signalling pathway in many organisms, as well as between pal-1 and caudal genes, both at the sequence and functional levels, these new roles for pal-1 and netrin may find resonance in other systems. Finally, this work has characterised the expression of a member of the C. elegans Hedgehog-related family of genes, wrt-2, in the epidermis and has provided insight into the possible functions of this gene in vivo.
Supervisor: Woollard, Alison Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available