Multiple Roles of Neurotrypsin in Tissue Morphogenesis and Nervous System Development Suggested by the mRNA Expression Pattern

University of Zurich, Zürich, Zurich, Switzerland
Molecular and Cellular Neuroscience (Impact Factor: 3.84). 11/2001; 18(4):407-33. DOI: 10.1006/mcne.2001.1029
Source: PubMed


We have mapped the spatio-temporal expression of the multidomain serine protease neurotrypsin in the developing mouse by in situ hybridization. On embryonic day (E) 8, mRNA is detected in giant trophoblast cells, later in embryonic mesenchymal tissues. On E11, expression begins in Schwann cell precursors, olfactory epithelium, trigeminal ganglion, and midbrain. The floor plate shows strong expression on E12. Further prenatal development is characterized by rising neurotrypsin mRNA in sensory ganglia and motor neurons. Staining in cerebral cortex emerges around birth and culminates toward the end of the first week with a complex laminar and areal pattern. Expression in peripheral nerves and nonneural tissues vanishes soon after birth and the adult neuronal distribution is gradually established until weaning age. This developmental expression pattern suggests roles of neurotrypsin in morphogenesis of nonneural tissues, as well as in neural development, in particular in axonal target invasion, synaptogenesis, and Schwann cell differentiation.

  • Source
    • "In contrast, motopsin is detected in the dendrites or the somatic body of neurons under normal expression levels (Mitsui et al., 2007). The expression of motopsin mRNA in the cerebral cortex culminates around the second week after birth (Iijima et al., 1997; Wolfer et al., 2001), then gradually decreases through the lifetime of an individual. This temporal expression pattern raises the additional possibility that motopsin may be involved in the development of the cerebral cortex. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Motopsin (prss12) is a mosaic serine protease that is secreted by neuronal cells and is believed to be important for cognitive function, as the loss of motopsin function causes severe nonsyndromic mental retardation. To understand the molecular role of motopsin, we identified the integral membrane protein 2a (Itm2a) as a motopsin-interacting protein using a yeast two-hybrid system. A pull-down assay revealed that the BRICHOS domain of Itm2a was essential for this interaction. Motopsin and Itm2a co-localized in COS cells and in cultured neurons when transiently expressed in these cells. Both proteins were co-immunoprecipitated from lysates of these transfected COS cells. Interestingly, Itm2a was strongly detected in a brain lysate prepared between postnatal day 0 and 10, during which period motopsin protein is also enriched in the brain. Immunohistochemical analysis led to the detection of Itm2a as patchy spots along endothelial cells of brain capillaries, which also expressed myosin II regulatory light chain (RLC), and on glial fibrillary acidic protein (GFAP)-positive processes in the developing cerebral cortex. Our results indicate the possibility that secreted motopsin interacts with endothelial cells in the developing brain.
    Preview · Article · Jan 2014 · Cell Biology International
    • "Neurotrypsin is secretion of neuronal cells in various brain regions, like hippocampus, cerebral cortex, and the cranial nerve nuclei.[1012] The mRNA of neurotrypsin is expressed most abundantly during the first postnatal week in the hippocampus and the cingulated cortex but its expression gradually decreases and still continues into adult life.[1213] The abundant expression of neurotrypsin mRNA During the perinatal period is observed in other regions as well, like olfactory system, cranial nerve nuclei, spinal cord, and peripheral nervous system, which suggest that neurotrypsin plays multiple roles in the developing nervous system.[14] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR) families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1). The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1)/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024) in vicinity of mental retardation (MR) locus (MRT1)/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.
    No preview · Article · Mar 2011 · Indian Journal of Human Genetics
  • Source
    • "PRSS12 (MIM: 606709), also known as neurotrypsin, was the first of such genes to be identified (Molinari et al. 2002). It encodes a trypsin-like serine protease, which is expressed in the embryo, and is likely involved in synapse maturation and neural plasticity (Molinari et al. 2002; Gschwend et al. 1997; Wolfer et al. 2001). It functions in the proteolytic cleavage of agrin at the synapse, which requires postsynaptic NMDAR activation (Matsumoto-Miyai et al. 2009; Stephan et al. 2008; Reif et al. 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Intellectual disability (ID), also referred to as mental retardation (MR), is frequently the result of genetic mutation. Where ID is present together with additional clinical symptoms or physical anomalies, there is often sufficient information available for the diagnosing physician to identify a known syndrome, which may then educe the identification of the causative defect. However, where co-morbid features are absent, narrowing down a specific gene can only be done by 'brute force' using the latest molecular genetic techniques. Here we attempt to provide a systematic review of genetic causes of cases of ID where no other symptoms or co-morbid features are present, or non-syndromic ID. We attempt to summarize commonalities between the genes and the molecular pathways of their encoded proteins. Since ID is a common feature of autism, and conversely autistic features are frequently present in individuals with ID, we also look at possible overlaps in genetic etiology with non-syndromic ID.
    Full-text · Article · Dec 2010 · Journal of Neurodevelopmental Disorders
Show more