Abstract
Congenital bladder anomalies are rare in newborns, but generally have severe outcomes that worsen during development. In this study, three rare congenital bladder disorders: bladder exstrophy (bladder exposed outside of the abdominal wall), neuropathic bladder (loss of neural control of bladder) and posterior urethral valves (PUV) disorder (an abnormally developed obstructive membrane in urethra that inhibits urine outflow) were investigated.Wnt signalling pathways, widely conserved in many species, play important roles in normal embryonic development. Disruption of these pathways potentially has a role in the formation of many anomalies and consequent functional disorders. It is hypothesised that disruption of Wnt-signalling pathways have some association with these bladder disorders.
Bladder tissue biopsies were collected from patients in Great Ormond Street Hospital for Sick Children with bladder exstrophy, neuropathic bladder and PUV disorders, as well as normal bladders. Intermediates in Wnt-signalling pathways (Wnt-related RNAs and proteins) were measured with mRNA and protein molecular imaging analysis.
The expression of Wnt-target proteins Pygo1, Cx43 and TCF7L1 were altered to different extents in exstrophy, neuropathic and PUV bladders compared to normal bladders. In addition, two groups of protein colocalisation (Pygo1/TCF7L1 and FRA1/TCF7L1) were detected in bladder exstrophy samples. Changes to similar mRNA targets were not detected in bladder anomaly targets. Overall the data indicate that changes to Wnt-signalling pathways are associated with anomalous bladder development and functionality.
| Date of Award | 28 Sept 2021 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Christopher J L G Fry (Supervisor), Dawn Davies (Supervisor) & Aamir Ahmed (Supervisor) |
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