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Molecular, cellular and developmental studies of sensory hyperinnervation following neonatal skin wounding.

Alvares, Debie Maria; (2000) Molecular, cellular and developmental studies of sensory hyperinnervation following neonatal skin wounding. Doctoral thesis (Ph.D.), University College London. Green open access

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Abstract

A close interaction exists between the nervous system and the skin during development and injury. During development target derived factors are important for patterning the neuronal elements present in later life. After injury, at critical developmental time points this patterning is subject to change for long periods, and can subsequently affect pain processing. Sensory hyperinnervation is profound in the skin of postnatal animals wounded at birth (Reynolds & Fitzgerald 1995). Here I have examined the development of this sensory hyperinnervation and the neurotrophins as possible causal factors. In vitro models for this phenomenon and histochemical characterisation of neurite outgrowth has also been assessed. NGF, NT-3 and GDNF are all upregulated after skin wounding in the above circumstance. However, neither NGF nor NT-3 are solely responsible for the hyperinnervation (Reynolds et al. 1997; Alvares et al. 1999). In vitro studies have demonstrated that NT-3 may be partly responsible, although trkC IgG fusion proteins show no effect in vivo. In vitro models have also demonstrated the importance of the dermis/epidermis for determining extent of neurite outgrowth. To add a new dimension to this study, I have constructed a neonatal wounded/naive skin cDNA library. By using a differential screening approach with mPCR probes, genes regulated in the above situation have been isolated. Clones generated have been sequenced and Northerns, and in situ hybridisation studies undertaken for genes of interest. Clones of particular interest include an endoplasmic reticulum stress protein-like gene (Erp29), an alpha globin-like gene, an ephrin (EPHRIN-A4) and a guanine nucleotide releasing protein-like gene. In addition several novel clones have been isolated which have yet to be characterised. This research will provide further information and understanding to both wound healing in neonates, and the peripheral patterning of cutaneous innervation during development, and lead to the discovery of the essence of hyperinnervation a largely unexplored event.

Type: Thesis (Doctoral)
Qualification: Ph.D.
Title: Molecular, cellular and developmental studies of sensory hyperinnervation following neonatal skin wounding.
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
URI: https://discovery.ucl.ac.uk/id/eprint/10108343
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