The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.

Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development / V. Insolia, E.C. Priori, C. Gasperini, F. Coppa, M. Cocchia, E. Iervasi, B. Ferrari, R. Besio, S. Maruelli, G. Bernocchi, A. Forlino, M.G. Bottone. - In: JOURNAL OF COMPARATIVE NEUROLOGY. - ISSN 0021-9967. - 528:1(2020), pp. 61-80. [10.1002/cne.24735]

Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development

E.C. Priori;
2020

Abstract

The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.
basement membrane; cerebellar development; cortical dysplasia; prolidase deficiency; Animals; Animals, Newborn; Cerebellar Cortex; Dipeptidases; Extracellular Matrix; Fluorescent Antibody Technique; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Mice, Transgenic
Settore BIO/06 - Anatomia Comparata e Citologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/902343
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