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The role of cell-surface neutral metalloendopeptidases in craniofacial development.

Spencer-Dene, Bradley; (1995) The role of cell-surface neutral metalloendopeptidases in craniofacial development. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

It is proposed that cell-surface zinc-dependent metalloendopeptidases, by virtue of their capacity to cleave and inactivate a wide range of peptide morphogens, represent a hitherto unrecognised level of control during growth and differentiation of the mammalian head and face. The spatio-temporal distributions of two of these enzymes, neutral endopeptidase (NEP) and endopeptidase-2 (Endo-2), have been demonstrated immunohistochemically. Their presence in a wide range of craniofacial tissues in the rat, during a gestational period when these tissues are undergoing active morphogenesis, suggests that these enzymes play key roles in the development of the craniofacial region. In addition, the patterns of expression of NEP mRNA have been described using in situ hybridization. In order to investigate the roles played by NEP, the activity of the endogenous enzyme was blocked using two chemically distinct, highly selective NEP inhibitors, during whole embryo culture. At the end of the culture period, the treated embryos exhibited a characteristic asymmetric craniofacial dysmorphogenesis. Histological examination revealed a distension of the left internal carotid and first branchial arch arteries. The predominantly prosencephalic swelling was considerably exacerbated by an overgrowth of the overlying neuroepithelium. In addition, there was often incomplete closure of the cranial neural folds, and the branchial arches were of a dysmorphic appearance on the affected side. From these studies it can be concluded that both NEP and Endo-2 are present during development of the embryonic rat head and face, and that NEP appears to be essential for normal morphogenesis of the craniofacial region.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of cell-surface neutral metalloendopeptidases in craniofacial development.
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/10105152
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