NG2-expressing cells in the subventricular zone are type C–like cells and contribute to interneuron generation in the postnatal hippocampus

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

Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone

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 wild-type 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

Propuesta de mejora para reducir los costos de producción de balerinas en la empresa de calzado Falbric SAC

RESUMEN Objetivo. Formular una propuesta de mejora para poder reducir los costos de producción en la empresa de calzado FALBRIC S.A.C en la provincia de Trujillo. Metodología. Investigación no experimental, transversal, descriptiva propositiva realizada a los trabajadores del área de producción y personal administrativa de la empresa. Se elaboró una encuesta con 10 preguntas, para poder encontrar los principales problemas que afectan los altos costos de producción, se usaron cuadros y gráficos estadísticos. Resultados. Obtuvimos que los principales problemas son la falta de control en el proceso productivo e indicadores de calidad determinando un costo de perdida de S/. 4,020.00; la falta de indicadores de producción con un costo de pérdida de s/ 652.33 soles; la falta de una planificación de la producción con un costo perdido anual de s/ 12,820.80 soles; la falta de capacitación para los trabajadores con un costo perdido anual de s/ 4,256.21 soles; la inadecuada planificación de adquisición de materiales y/o insumos para el procesos productivo con una pérdida de s/ 6,380.61 soles y por último la ausencia de personal experimentado con un costo de pérdida anual de s/ 4,800.00 soles. Conclusiones. Para los problemas encontrados proponemos las siguientes herramientas de mejora respectivamente Análisis de Modo y Efecto de fallas, Kanban, MRP I, MRP II, Plan de Capacitación y un Análisis de Perfil de Puesto. PALABRAS CLAVE: empresa de calzado, costos de producción, propuesta de mejora

TGFβ signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1

Research on myelination has focused on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. Here, we show that transforming growth factor β (TGFβ) signaling is crucial for allowing oligodendrocyte progenitor (OP) cell cycle withdrawal, and therefore, for oligodendrogenesis and postnatal CNS myelination. Enhanced oligodendrogenesis and subcortical white matter (SCWM) myelination was detected after TGFβ gain of function, while TGFβ receptor II (TGFβ-RII) deletion in OPs prevents their development into mature myelinating OLs, leading to SCWM hypomyelination in mice. TGFβ signaling modulates OP cell cycle withdrawal and differentiation through the transcriptional modulation of c-myc and p21 gene expression, mediated by the interaction of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the first to demonstrate an autonomous and crucial role of TGFβ signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases.National Institutes of Health (NIH)National Multiple Sclerosis SocietyMinisterio de EducaciónDepto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu

The ventricular-subventricular zone: a source of oligodendrocytes in the adult brain

Demyelinating diseases are characterized by an extensive loss of oligodendrocytes and myelin sheaths from axolemma, which commonly result in disability in young adults. To date, there is no effective treatment against these neurological disorders. In the adult brain, there are neural stem cells (NSCs) that reside within a niche denominated ventricular-subventricular zone (V-SVZ) in the lateral wall of the cerebral ventricles. NSCs give rise to neurons and oligodendrocytes that help preserve cellular homeostasis. Growing evidence indicates that V-SVZ progenitor cells may represent an endogenous source of oligodendrocytes that can be useful to treat demyelinating diseases. This e-Book collected the most recent evidence regarding the mechanisms that modulate the proliferation, migration, quiescence, cell-fate choices and survival of oligodendrocyte precursors generated in the V-SVZ. Herein, we compiled information about the role of Sonic hedgehog, NMDA receptors, ErbB proteins, hemopressin, erythropoietin, osmolarity and microglia in the oligodendrocyte production. Some chapters also describe the role of oligodendrocyte precursors in the preservation of cellular homeostasis, aging and white matter repair. All these information is presented as novel research findings, short communications, and review articles, which were written by experts in the field of oligodendrocyte generation, myelin production and white matter re-myelination

Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17

The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair. SIGNIFICANCE STATEMENT Oligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPs in vivo overcomes the defects in OL development during postnatal development but also OL regeneration during CNS remyelination. Our study identifies TACE as an essential player in OL regeneration that may provide new insights in the development of new strategies for promoting myelin repair in demyelinating disorders