Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression

In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis

The neurogenic potential of astrocytes is regulated by inflammatory signals

Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes

The obstacles to teacher training created by the conceptions which prospective teachers have of science, teaching and learning

Les croyances du corps enseignant sur la nature des connaissances en général et, en particulier, sur les connaissances scientifiques ont un rapport direct avec la façon de comprendre et d'enseigner les sciences. Elles constituent fréquemment de véritables obstacles à la formation professionnelle des professeurs et à une réelle amélioration des processus d'enseignement: apprentissage. Dans cette optique, nous mettons d'abord en évidence la diversité des conceptions scientifiques et didactiques des professeurs détectées par un certain nombre d'études. Sur la base de nos propres résultats, nous proposons différents niveaux de formulation des connaissances professionnelles dans le but d'orienter le processus de formation ; nous précisons les obstacles associés aux conceptions, les plus fréquentes parmi les professeurs et qui, pour nous formateurs, constituent les axes de notre intervention ; et pour conclure nous ne ferons que citer quelques implications de ce qui précède dans la formation du corps enseignant

Otro título: Tertulia Literaria Hispanoamericana. Sesión 786, 18 de noviembre de 1975

Alberto Porlan. Rafael MontesinosAlberto Porlan explica que la obra de Alberto E. Mazzocchi nunca llamó la atención a ningún crítico y a ningún editor y que el mismo Alberto murió sin saber de su edición. No son mucho versos pero sí para lo joven que murió y lee algunos -- Min. 04.52: Raros son todos raros -- Min. 13.01: Alberto ofrece una biografía de Mazzocchi -- Min. 16.19: Tengo que viajar como todos los que viajan a altas horas de la noche -- Min. 18.37: Continuación de su biografía -- Min. 19.17: Lectura del texto de la invitación de su boda -- Min. 26.35: Biografía sobre su matrimonio -- Min. 27.56: Alberto Porlan cuanta como Max Born, llamado en realidad Federico Mundiano, amigo de Mazzocchi que se ha encargado de recopilar, guardar y dar a conocer toda la obra de Mazzocchi y pasa a leer algunos de esos poemas -- Min. 30.34: No se porqué se debe morir -- Min. 43.38: Rafael Montesinos da inicio al coloquio -- Min. 56.46: Montesinos de despide y presenta a Olga Elena para la siguiente tertuli

MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.

The identification of mechanisms that maintain stem cell niche architecture and homeostasis is fundamental to our understanding of tissue renewal and repair. Cell adhesion is a well-characterized mechanism for developmental morphogenetic processes, but its contribution to the dynamic regulation of adult mammalian stem cell niches is still poorly defined. We show that N-cadherin-mediated anchorage of neural stem cells (NSCs) to ependymocytes in the adult murine subependymal zone modulates their quiescence. We further identify MT5-MMP as a membrane-type metalloproteinase responsible for the shedding of the N-cadherin ectodomain in this niche. MT5-MMP is co-expressed with N-cadherin in adult NSCs and ependymocytes and, whereas MT5-MMP-mediated cleavage of N-cadherin is dispensable for the regulation of NSC generation and identity, it is required for proper activation of NSCs under physiological and regenerative conditions. Our results indicate that the proliferative status of stem cells can be dynamically modulated by regulated cleavage of cell adhesion molecules

Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives

Neural stem cell quiescence comes to an un-sticky end

Cell-cell interactions, a key feature of the stem cell niche, regulate many aspects of stem cell behaviour. N-cadherin-mediated anchorage of neural stem cells within the adult neural niche maintains stem cell quiescence, and its release by the metalloproteinase MT5-MMP promotes neural stem cell activation

Formação docente: reflexões sobre o estágio curricular

O presente artigo apresenta reflexões e discussões sobre a importância e o papel do estágio curricular na formação prática de alunos do curso de licenciatura em Ciências Biológicas. A partir da análise do estágio curricular dos acadêmicos do 7º e 9º período, foram identificados os aspectos favoráveis e desfavoráveis e formuladas sugestões que visam melhorar a qualidade do mesmo. A pesquisa acerca da realidade e dos problemas do estágio supervisionado foi realizada por meio de análise documental (diário de campo e narrativas) e questionários. Com auxílio da literatura especializada, conseguimos aprofundar a compreensão dos mecanismos de articulação entre teoria e prática no cotidiano escolar, o que poderá contribuir para a construção de um currículo mais coerente com a realidade da sala de aula da Educação Básica