References of "Gallo, Vittorio"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system.
Caillava, Céline; Vandenbosch, Renaud ULg; Jablonska, Beata et al

in Journal of Cell Biology (2011), 193(2), 397-407

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but ... [more ▼]

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2(-/-) mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin. [less ▲]

Detailed reference viewed: 25 (13 ULg)
Full Text
Peer Reviewed
See detailCdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone
Jablonska, Beata; Aguirre, Adan A.; Vandenbosch, Renaud ULg et al

in Journal of Cell Biology (2007), 179(6), 1231-1245

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the ... [more ▼]

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2(-/-) and wild-type mice at perinatal ages and are reduced only in adult Cdk2(-/-) mice. Adult Cdk2(-/-) SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2(-/-) SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2(-/-) cells coincides with lower NG2(+) proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2(-/-) SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wildtype levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4. [less ▲]

Detailed reference viewed: 31 (7 ULg)
Full Text
Peer Reviewed
See detailCdk2 Is Dispensable for Adult Hippocampal Neurogenesis
Vandenbosch, Renaud ULg; Borgs, Laurence ULg; Beukelaers, Pierre ULg et al

in Cell Cycle (Georgetown, Tex.) (2007), 6(24), 3065-9

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of ... [more ▼]

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2(-/-) mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis. [less ▲]

Detailed reference viewed: 105 (18 ULg)
Full Text
Peer Reviewed
See detailIdentification of Sox17 as a transcription factor that regulates oligodendrocyte development
Sohn, Jiho; Natale, Joanne; Chew, Li-Jin et al

in Journal of Neuroscience (2006), 26(38), 9722-9735

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2', 3'- cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein ... [more ▼]

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2', 3'- cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17 (SRY-box containing gene 17) gene expression to be coordinately regulated with that of four myelin genes during postnatal development. In CNP-EGFP-positive (CNP-EGFP(+)) cells, Sox17 mRNA and protein levels transiently increased between postnatal days 2 and 15, with white matter O4(+) preoligodendrocytes expressing greater Sox17 levels than Nkx2.2(+) ( NK2 transcription factor related, locus 2) NG2(+), or GalC(+) ( galactocerebroside) cells. In spinal cord, Sox17 protein expression was undetectable in the primary motor neuron domain between embryonic days 12.5 and 15.5 but was evident in Nkx2.2(+) and CCl+ cells. In cultured oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4(+) cells and peaked during the phenotypic conversion from bipolar to multipolar. Parallel increases in Sox17 and p27 occurred before MBP protein expression, and Sox17 upregulation was prevented by conditions inhibiting differentiation. Sox17 down-regulation with small interfering RNAs increased OPC proliferation and decreased lineage progression after mitogen withdrawal, whereas Sox17 overexpression in the presence of mitogen had opposite effects. Sox17 overexpression enhanced myelin gene expression in OPCs and directly stimulated MBP gene promoter activity. These findings support important roles for Sox17 in controlling both oligodendrocyte progenitor cell cycle exit and differentiation. [less ▲]

Detailed reference viewed: 25 (4 ULg)
Full Text
Peer Reviewed
See detailThe Yin and Yang of cell cycle progression and differentiation in the oligodendroglial lineage
Nguyen, Laurent ULg; Borgs, Laurence ULg; Vandenbosch, Renaud ULg et al

in Mental Retardation & Developmental Disabilities Research Reviews (2006), 12(2), 85-96

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor ... [more ▼]

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white matter, contact the axon, and differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie the eventual progressive deterioration that typifies the natural history of developmental demyelination in LID and PVL and of adult-onset demyelination in MS. Over the past few years, pathophysiological studies have mostly focused on seeking abnormalities that impede oligodendroglial maturation at the level of migration, myelination, and survival. In contrast, there has been a strikingly lower interest for early proliferative and differentiation events that are likely to be equally critical for white matter development and myelin repair. This review highlights the Yin and Yang principles of interactions between intrinsic factors that coordinately regulate progenitor cell division and the onset of differentiation, i.e. the initial steps of oligodendrocyte lineage progression that are obviously crucial in health and diseases. (C) 2006 Wiley-Liss, Inc. [less ▲]

Detailed reference viewed: 58 (4 ULg)
Full Text
Peer Reviewed
See detailShaker-type potassium channel subunits differentially control oligodendrocyte progenitor proliferation
Vautier, Francois; Belachew, Shibeshih ULg; Chittajallu, Ramesh et al

in Glia (2004), 48(4), 337-345

Oligodendrocyte precursor (OP) cells are exposed to multiple extrinsic signals that control their proliferation and differentiation. Previous cell proliferation studies and electrophysiological analysis ... [more ▼]

Oligodendrocyte precursor (OP) cells are exposed to multiple extrinsic signals that control their proliferation and differentiation. Previous cell proliferation studies and electrophysiological analysis in cultured cells and in brain slices have suggested that outward potassium channels, particularly Kv1 subunits, may have a prominent role in OP cell proliferation. In the present study, we assessed to what extent overexpression of Kv1.3, Kv1.4, Kv1.5, and Kv1.6 can affect OP cell proliferation and differentiation in culture. We observed that overexpression of Kv1.3 or Kv1.4 increased OP cell proliferation in the absence of mitogens, whereas Kv1.6 overexpression inhibited mitogen-induced OP cell cycle progression. Interestingly, Kv1.3, Kv1.4, Kv1.5, and Kv1.6 overexpression did not interfere with the kinetics of oligodendrocyte differentiation. This study represents the first demonstration that the activity of potassium channels containing distinct Kv1 subunit proteins directly controls oligodendroglial proliferation in the presence of mitogens, as well as in growth factor-free conditions. (C) 2004 Wiley-Liss, Inc. [less ▲]

Detailed reference viewed: 34 (2 ULg)
Full Text
Peer Reviewed
See detailSynaptic and extrasynaptic neurotransmitter receptors in glial precursors' quest for identity
Belachew, Shibeshih ULg; Gallo, Vittorio

in Glia (2004), 48(3), 185-196

It is widely established that neurotransmitter receptors are expressed in non-neuronal cells, and particularly in neural progenitor cells in the postnatal central nervous system. The functional role of ... [more ▼]

It is widely established that neurotransmitter receptors are expressed in non-neuronal cells, and particularly in neural progenitor cells in the postnatal central nervous system. The functional role of these receptors during development is unclear, but it needs to be revisited now that cells previously considered restricted to glial lineages have been shown to generate neurons. The present review integrates recent advances, to shed new light on how neurotransmitter receptors may, alternatively, serve as excitable mediators of neuron-glia and neuron-neuroblast interactions. (C) 2004 Wiley-Liss, Inc. [less ▲]

Detailed reference viewed: 12 (2 ULg)
Full Text
Peer Reviewed
See detailNG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus
Aguirre, Adan A.; Chittajallu, Ramesh; Belachew, Shibeshih ULg et al

in Journal of Cell Biology (2004), 165(4), 575-589

The subventricular zone (SVZ) is a source of neural progenitors throughout brain development. The identification and purification of these progenitors and the analysis of their lineage potential are ... [more ▼]

The subventricular zone (SVZ) is a source of neural progenitors throughout brain development. The identification and purification of these progenitors and the analysis of their lineage potential are fundamental issues for future brain repair therapies. We demonstrate that early postnatal NG2-expressing (NG2(+)) progenitor cells located in the SVZ self-renew in vitro and display phenotypic features of transit-amplifier type C-like multipotent cells. NG2(+) cells in the SVZ are highly proliferative and express the epidermal growth factor receptor, the transcription factors Dlx, Mash1, and Olig2, and the Lewis X (LeX) antigen. We show that grafted early postnatal NG2(+) cells generate hippocampal GABAergic interneurons that propagate action potentials and receive functional glutamatergic synaptic inputs. Our work identifies Dlx(+)/Mash1(+)/LeX(+)/NG2(+)/GFAP-negative cells of the SVZ as a new class of postnatal multipotent progenitor cells that may represent a specific cellular reservoir for renewal of postnatal and adult inhibitory interneurons in the hippocampus. [less ▲]

Detailed reference viewed: 38 (4 ULg)
Full Text
Peer Reviewed
See detailPostnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.
Belachew, Shibeshih ULg; Chittajallu, Ramesh; Aguirre, Adan A. et al

in Journal of Cell Biology (2003), 161(1), 169-86

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using ... [more ▼]

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis. [less ▲]

Detailed reference viewed: 25 (3 ULg)
Full Text
Peer Reviewed
See detailCyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors.
Belachew, Shibeshih ULg; Aguirre, Adan A.; Wang, Hang et al

in Journal of Neuroscience (2002), 22(19), 8553-62

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E ... [more ▼]

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E/cyclin-dependent kinase-2 (cdk2) activity. To establish a causal link between cyclin E/cdk2 activity and OP proliferation, we selectively modulated cdk2 activity in vitro by transfection of cultured OP cells. Dominant-negative (Dn)-cdk2 overexpression inhibited mitogen-induced OP cell proliferation, whereas wild-type (wt)-cdk2 prevented cell cycle arrest caused by anti-mitotic signals. Dn-cdk2- or wt-cdk2-mediated regulation of G(1)/S transition, per se, did not influence initiation of OP differentiation. To study the function of cyclin E/cdk2 in OP cells during development in vivo, we analyzed cdk2 and cyclin E expression in cells acutely isolated from transgenic mice expressing the green fluorescent protein (GFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase gene promoter. Both cyclin E/cdk2 protein levels and activity were decreased in GFP(+) oligodendrocyte lineage cells between postnatal days 4 and 30. Immunostaining of NG2(+)/GFP(+) OP cells in brain tissue sections showed a 90% decrease in overall cell proliferation and cdk2 expression between perinatal and adult cells. However, cdk2 expression within the proliferating (i.e., expressing the proliferating cell nuclear antigen) OP cell population was maintained throughout development. Our data indicate that: (1) cyclin E/cdk2 activity plays a pivotal function in OP cell cycle decisions occurring at G(1)/S checkpoint; (2) initiation of OP differentiation is independent of cyclinE/cdk2 checkpoint, and (3) intrinsic differences in cyclin E/cdk2 expression and activity may underlie the slowly proliferative state that characterizes so-called "quiescent" adult OP cells in vivo. [less ▲]

Detailed reference viewed: 20 (1 ULg)
Full Text
Peer Reviewed
See detailExpression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies.
Yuan, Xiaoqing; Chittajallu, Ramesh; Belachew, Shibeshih ULg et al

in Journal of Neuroscience Research (2002), 70(4), 529-45

We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized ... [more ▼]

We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized in live tissue throughout embryonic and postnatal development. Immunohistochemical analysis in brain tissue and in sciatic nerve demonstrated that EGFP expression was restricted to cells of the oligodendrocyte and Schwann cell lineages. EGFP was also strongly expressed in "adult" oligodendrocyte progenitors (OPs) and in gray matter oligodendrocytes. Fluorescence-activated cell sorting allowed high-yield purification of EGFP(+) oligodendrocyte-lineage cells from transgenic brains. Electrophysiological patch clamp recordings of EGFP(+) cells in situ demonstrated that OP cells displayed large outward tetraethylammonium (TEA)-sensitive K(+) currents and very small inward currents, whereas mature oligodendrocytes were characterized by expression of large inward currents and small outward K(+) currents. The proliferation rate of EGFP(+) cells in developing white matter decreased with the age of the animals and was strongly inhibited by TEA. Oligodendrocyte development and physiology can be studied in live tissue of CNP-EGFP transgenic mice, which represent a source of pure EGFP(+) oligodendrocyte-lineage cells throughout development. [less ▲]

Detailed reference viewed: 52 (5 ULg)
Full Text
Peer Reviewed
See detailUnraveling Oligodendrocyte Origin and Function by Cell-Specific Transgenesis
Belachew, Shibeshih ULg; Yuan, Xiaoqing; Gallo, Vittorio

in Developmental Neuroscience (2001), 23(4-5), 287-98

Besides the role of mature oligodendrocytes in myelin synthesis during the development of the central nervous system (CNS), the oligodendrocyte lineage also encompasses the largest pool of postnatal ... [more ▼]

Besides the role of mature oligodendrocytes in myelin synthesis during the development of the central nervous system (CNS), the oligodendrocyte lineage also encompasses the largest pool of postnatal proliferating progenitors whose behavior in vivo remains broadly elusive in health and disease. We describe here transgenic models that allow us to track the functions and origins of such cells by using proteolipid protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) gene promoters to direct oligodendroglial expression of different reporters, in particular the green fluorescent protein (GFP). We emphasize that the CNP-GFP mouse, which targets the entire oligodendroglial lineage from embryonic life to adulthood, provides an outstanding tool to study the in vivo properties of oligodendrocyte progenitor cells in normal and damaged CNS. [less ▲]

Detailed reference viewed: 18 (2 ULg)