Umberto Di Porzio

Researcher of Neuroscience, Former Director

Name Umberto
Surname Di Porzio
Institution CNR - IGB "Adriano Buzzati Traverso"
Telephone +39 081 6132356
E-Mail umberto.diporzio@igb.cnr.it
Address Institute of Genetics and Biophysics – ABT Via Pietro Castellino 111 – 80131 Napoli, Italy
Umberto Di Porzio

Member PUBLICATIONS

  • Chronic activation of ERK and neurodegenerative diseases.

    Publication Date: 01/11/2003 on BioEssays : news and reviews in molecular, cellular and developmental biology
    by Colucci-D'Amato L, Perrone-Capano C, di Porzio U
    DOI: 10.1002/bies.10355

    The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dictates its subcellular compartmentalization and/or trafficking. The latter, in turn, dictates whether ERK-expressing cells would enter a program of cell death, survival or differentiation. We summarize experimental data showing that chronic activation of ERK plays a role in the mechanisms that trigger neurodegeneration. We also discuss how MKPs, members of the subclass of dual specificity phosphatases, might be the link between ERK kinetics and its subcellular localization.

  • Ontogeny of kainate receptor gene expression in the developing rat midbrain and striatum.

    Publication Date: 15/07/2002 on Brain research. Molecular brain research
    by Lilliu V, Perrone-Capano C, Pernas-Alonso R, Diaz Trelles R, Luca Colucci d'Amato G, Zuddas A, di Porzio U

    Kainate (KA) receptors are a family of ionotropic glutamate receptors, which mediate the excitatory synaptic transmission in various areas of the mammalian CNS. We have studied the expression pattern of the genes encoding for KA receptor subunits (Glur5-1, Glur5-2, Glur6, Glur7, KA1 and KA2) in rat prenatal (E), postnatal and adult ventral mesencephalon (MES) and striatum (STR) and in fetal midbrain primary cultures. Each receptor subunit shows a unique area- and temporal-expression pattern. In MES the onset of both Glur5 subunits is delayed when compared to the other subunits. In addition, most of the transcripts for KA subunits gradually increase during embryonic development and show a slight decrease during the first postnatal week. Differently, Glur6 and KA2 mRNAs show a sharp increase at E14.5 and decrease thereafter, reaching the lowest levels during late embryonic and postnatal development. In the STR, the gene expression of all KA subunit mRNAs is higher during embryonic development than after birth, except KA1 transcripts, that show a peak at P5. In embryonic MES primary cultures, Glur5-2, Glur6 and KA2 mRNAs are higher at the beginning of the culture when compared to older cultures, while the other subunit mRNAs do not show significant variation throughout the days in vitro. Thus, all the KA receptor subunit transcripts appear independently regulated during MES and STR development, probably contributing to the establishment of the fine tuning of the excitatory circuits reciprocally established between these CNS areas.

  • Ontogeny of AMPA receptor gene expression in the developing rat midbrain and striatum.

    Publication Date: 30/11/2001 on Brain research. Molecular brain research
    by Lilliu V, Pernas-Alonso R, Trelles RD, di Porzio U, Zuddas A, Perrone-Capano C

    AMPA receptors mediate most of the fast excitatory synaptic transmission in the mammalian CNS. Their ontogeny during embryonic (E) and postnatal (P) development is still poorly understood. We have studied the expression of the genes encoding for AMPA glutamate receptor subunits (GlurA, GlurB, GlurC and GlurD) in the rat ventral mesencephalon (MES) and striatum (STR) and in fetal midbrain primary cultures. Each receptor subunit shows unique area- and temporal-expression pattern. In MES, GluRA, GlurB and GlurC mRNA are detectable from the earliest embryonic stage studied (E13) and raise thereafter between E15 and E17, to plateau at E19 to adult values. Differently, GlurD mRNA increases throughout embryonic and postnatal development reaching its highest levels in the adult MES. The pattern of AMPA proteins corresponded to the mRNA levels for all subunits. In the STR, GlurA gene expression increases between E15 and E19, GlurB mRNA levels are sustained from the first embryonic stages analyzed (E15) until E19 and gradually decrease thereafter toward adult levels, GlurC gene expression increases gradually throughout ontogeny to reach its highest levels in the adult. STR GlurD transcripts remain at constant levels in all stages studied. In embryonic MES primary cultures, every subunit show a characteristic expression profile similar to that observed in vivo. They all decrease significantly during the second week in vitro. Thus, all the AMPA receptor subunit transcripts appear independently regulated during development, probably depending on the tissue-specific environment, which seems preserved in MES cultures.

  • Regionalized neurofilament accumulation and motoneuron degeneration are linked phenotypes in wobbler neuromuscular disease.

    Publication Date: 01/08/2001 on Neurobiology of disease
    by Pernas-Alonso R, Perrone-Capano C, Volpicelli F, di Porzio U
    DOI: 10.1006/nbdi.2001.0403

    Abnormal neurofilament aggregates are pathological hall-mark of most neurodegenerative diseases, although their pathogenic role remains unclear. Increased expression of medium neurofilament (NFM) is an early molecular marker of wobbler mouse, an animal model of motoneuron disease. In the wr/wr, a vacuolar neuronal degeneration (VND) starts at 15 days postnatally, selectively in cervical spinal cord and brain stem motoneurons. Here we show that nfm gene hyperexpression is restricted to the aforementioned motoneurons and is specific for wr mutation. NF proteins accumulate in wr/wr before VND. wr/+ mice, which are asymptomatic, show intermediate NF accumulation between wr/wr and +/+ littermates, suggesting a gene dosage dependence of the wobbler pathology. Altogether our data indicate that NF hyperexpression and regionalized motoneuron degeneration are linked to the wr mutation, although with a still unknown relationship to the mutant gene activity.

  • Neurofilament homeostasis and motoneurone degeneration.

    Publication Date: 01/01/2001 on BioEssays : news and reviews in molecular, cellular and developmental biology
    by Perrone Capano C, Pernas-Alonso R, di Porzio U
    DOI: 10.1002/1521-1878(200101)23:1<24::AID-BIES1004>3.0.CO;2-H

    Neurofilament disorganisation is a hallmark of various neurodegenerative diseases. We review here current knowledge of neurofilament structure, gene expression and function. Neurofilament involvement in motoneurone neurological diseases is discussed in view of recent data from transgenic and spontaneous mouse mutants. In the mammalian neurone, the three neurofilament subunits are assembled into intermediate filaments as obligate heteropolymers. The subunits are expressed differentially during development and adult life according to the cell type and its physiological state. In addition to the well-established role of neurofilaments in the control of axonal calibre, there is increasing evidence that neurofilaments can interact with other cytoskeletal components and can modulate the axoplasmic flow. Although the extent to which neurofilament abnormalities contribute to the pathogenesis in human diseases remains unknown, emerging evidence suggests that disorganised neurofilaments can provoke degeneration and death of neurones. BioEssays 23:24-33, 2001.

  • Genetic and epigenetic control of midbrain dopaminergic neuron development.

    Publication Date: 01/01/2000 on The International journal of developmental biology
    by Perrone-Capano C, Di Porzio U

    The relatively few dopaminergic (DA) neurons in the mammalian brain regulate many important neural functions, including motor integration, neuroendocrine hormone release, cognition, emotive behaviors and reward. A number of laboratories, including ours, have contributed to unravel the mechanisms of DA phenotype induction and maturation and elucidated the role of epigenetic factors involved in specification, development and maintenance of midbrain dopaminergic functions. DA progenitors are first "committed" to give rise to DA neurons by the action of two secreted factors, Sonic hedgehog and fibroblast growth factor 8 (FGF8). Subsequently, the function of selectively activated transcription factors, Nurr1 and Ptx3, is required for the DA final determination. Further development of DA neurotransmission requires specific interactions with the developing target striatal cells, which modulate key DA functions, namely synthesis and uptake of the neurotransmitter. Committed and determined DA neurons express the key genes involved in DA neurotransmission at different times in development. In rodents, synthesis and intracellular accumulation of DA is achieved shortly after expression of Nurr1, while the onset of high affinity uptake, responsible for ending the neurotransmission, takes place after a few days. Cell contacts between the presynaptic DA neurons and target striatal neurons are apparently necessary for the fine modulation of DA function, in vivo and in vitro. Strikingly, the in situ maturation and phenotypic specialization of DA neurons grafted into the adult striatum/caudate-putamen parallels the normal development of committed fetal dopamine neurons during neurogenesis. The correct matching between the right presynaptic and postsynaptic neurons is required also for grafted DA cells.

  • Epigenetic cues in midbrain dopaminergic neuron development.

    Publication Date: 01/01/2000 on Neuroscience and biobehavioral reviews
    by Perrone-Capano C, Da Pozzo P, di Porzio U

    Midbrain dopaminergic (DA) neurons subserve complex and varied neural functions in vertebrate CNS. Their progenitors give rise to DA neurons by the action of two extracellular inducers, Sonic Hedgehog and FGF8. After this first commitment, the function of selectively activated transcription factors, like the orphan steroid nuclear receptor Nurr1, is required for DA final determination. Subsequently, DA function is selectively modulated by specific interaction with the developing striatal target tissue. Committed and determined DA neurons express the key genes involved in DA neurotransmission at different times in development. Synthesis and intracellular accumulation of DA is achieved shortly after expression of Nurr1, while high affinity uptake, responsible for ending the neurotransmission, takes place after a few days. Cell contacts between the presynaptic DA neurons and target striatal neurons are apparently necessary for the fine modulation of DA function, in vivo and in vitro.

  • Multiplex semi-quantitative reverse transcriptase-polymerase chain reaction of low abundance neuronal mRNAs.

    Publication Date: 01/12/1999 on Brain research. Brain research protocols
    by Pernas-Alonso R, Morelli F, di Porzio U, Perrone-Capano C

    The sequential use of reverse transcriptase and the polymerase chain reaction (RT-PCR) has provided molecular biology research with an exquisitely sensitive and fast technique for studying gene expression. This method is particularly useful to study transcripts in the nervous system, which are on average present at low levels and the amount of tissue or cells to be analyzed is often limited. Here, we describe a RT-PCR assay which allows the simultaneous detection and semi-quantitation of several transcripts (multiplex). Multiple PCR primer pairs are used to detect different target transcripts in a single reaction, together with a pair of primers able to amplify the hypoxantine-phosphoribosyl-transferase (HPRT), a gene constitutively expressed at low levels throughout the nervous system. HPRT levels remain constant also during neurogenesis and it is thus apt to be used in developmental neurobiology. This internal standard is the mRNA of reference to evaluate sample variation in RT and PCR reactions and to monitor the degradation and recovery of RNAs. Normalization with respect to HPRT cDNA allows to estimate the relative abundance of each target mRNA.

  • Neuronal and glial properties coexist in a novel mouse CNS immortalized cell line.

    Publication Date: 01/11/1999 on Experimental cell research
    by Colucci-D'Amato GL, Tino A, Pernas-Alonso R, ffrench-Mullen JM, di Porzio U
    DOI: 10.1006/excr.1999.4636

    A mes-c-myc A1 (A1) cell line was generated by retroviral infection of cultured embryonic mesencephalic cells and selected by neomycin resistance. A1 cells cease to divide and undergo morphological differentiation after serum withdrawal or addition of c-AMP. Proliferating or morphologically differentiated A1 cells are all positive for vimentin and nestin, a marker of neural precursor, and show neuronal markers such as microtubule-associated protein 1, neuron-specific enolase and peripherin, and the glial marker glial fibrillary acidic protein. Neuronal and glial markers coexist in single cells. Furthermore, A1 cells show presence of glutamic acid decarboxylase 67 mRNA and its embryonic form EP10 and accumulate the neurotransmitter GABA. Electrophysiological studies demonstrate that morphologically differentiated A1 cells display voltage-gated sodium and potassium channels in response to depolarizing stimuli. A1 cells thus represent a novel, bipotent neural cell line useful for studying CNS differentiation and plasticity, as well as the molecular mechanisms underlying development of GABAergic neurotransmission.

  • Epigenetic factors and midbrain dopaminergic neurone development.

    Publication Date: 01/10/1996 on BioEssays : news and reviews in molecular, cellular and developmental biology
    by Perrone-Capano C, di Porzio U
    DOI: 10.1002/bies.950181008

    In the mammalian brain dopamine systems play a central role in the control of movement, hormone release, emotional balance and reward. Alteration of dopaminergic neurotransmission is involved in Parkinson's disease and other movement disorders, as well as in some psychotic syndromes. This review summarises recent findings, which shed some light on signals and cellular interactions involved in the specification and maturation of the dopaminergic function during neurogenesis. In particular we will focus on three major issues: (1) the differentiation of dopaminergic neurones triggered by direct contact with the midbrain floor plate cells through the action of sonic hedgehog; (2) the neurotrophic factors acting on dopaminergic neurones; and (3) the role of target striatal cells on the survival and the axonal growth of developing or grafted dopaminergic neurones.