Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.694146
Title: Analysis of cd9b in CXCR4b signalling
Author: Greaves, Sarah Jennifer
ISNI:       0000 0004 5990 1559
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Abstract:
CXCR4b, CXCR7b and their ligand, CXCL12a, are essential for the migration of the posterior lateral line primordium (pLLP) and primordial germ cells (PGCs) in zebrafish (Dambly-Chaudière et al. 2007, Boldajipour et al. 2008). A number of tetraspanins have been shown to affect CXCR4-mediated processes through regulating CXCR4 trafficking or downstream signalling (Yoshida et al. 2008, Li et al. 2011, Leung et al. 2011). Based upon these results we set out to identify candidate tetraspanins that may play a similar role in CXCR4b signalling during pLLP and PGC migration. CD9b, one of the zebrafish homologs of human CD9, was identified as a good candidate gene. Morpholino knock down of cd9b, using either a translation-blocking or splice-site blocking morpholino, resulted in reduced neuromast deposition and abnormal structure of the posterior lateral line. However, morpholinos often have nonspecific effects and so two CD9b knockout lines were created using TALENs. Surprisingly CD9b homozygous mutants showed normal lateral line structure. Preliminary results suggest that the phenotype differences between CD9b morphants and mutants may be due to residual functionality in the wildtype N-terminal of CD9b, upstream of the mutation site, in CD9b mutants. As well as assessment of PGC and pLLP migration, CD9b mutants were also assessed for fertility defects. Significantly reduced numbers of pups are born to CD9 knockout mice. This is due to a requirement of CD9 on the egg membrane for efficient sperm-egg fusion in the CD9-/- female mice (Kaji et al. 2000, Le Naour et al. 2000, Miyado et al. 2000). CD9b -/- zebrafish also appear to have fertility defects. Fewer eggs were laid by CD9b -/- zebrafish pairs and of the eggs laid, a lower percentage were fertilised.
Supervisor: Roehl, H. ; Partridge, L. ; Monk, P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.694146  DOI: Not available
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