Navegando por Autor "Chouchane, Malek"
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Artigo Instructing neuronal identity during CNS development and astroglial-lineage reprogramming: Roles of NEUROG2 and ASCL1(Brain Research, 2018-03-03) Chouchane, Malek; Costa, Marcos RomualdoThe adult mammalian brain contains an enormous variety of neuronal types, which are generally categorized in large groups, based on their neurochemical identity, hodological properties and molecular markers. This broad classification has allowed the correlation between individual neural progenitor populations and their neuronal progeny, thus contributing to probe the cellular and molecular mechanisms involved in neuronal identity determination during central nervous system (CNS) development. In this review, we discuss the contribution of the proneural genes Neurogenin2 (Neurog2) and Achaete-scute homolog 1 (Ascl1) for the specification of neuronal phenotypes in the developing neocortex, cerebellum and retina. Then, we revise recent data on astroglia cell lineage reprogramming into induced neurons using the same proneural proteins to compare the neuronal phenotypes obtained from astroglial cells originated in those CNS regions. We conclude that Ascl1 and Neurog2 have different contributions to determine neuronal fates, depending on the neural progenitor or astroglial population expressing those proneural factors. Finally, we discuss some possible explanations for these seemingly conflicting effects of Ascl1 and Neurog2 and propose future approaches to further dissect the molecular mechanisms of neuronal identity specification.Artigo Lineage Reprogramming of Astroglial Cells from Different Origins into Distinct Neuronal Subtypes(2017-07) Chouchane, Malek; Faria, Ana Raquel Melo de; Moura, Daniela Maria de Souza; Hilscher, Markus Michael; Schroder, Timm; Leão, Richardson Naves; Costa, Marcos RomualdoAstroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs) in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2) or Achaete scute homolog-1 (Ascl1). We show that cerebellum (CerebAstro) and cerebral cortex astroglia (CtxAstro) generates iNs with distinctive neurochemical and morphological properties. Both astroglial populations contribute iNs to the olfactory bulb following transplantation in the postnatal and adult mouse subventricular zone. However, only CtxAstro transfected with Neurog2 differentiate into pyramidal-like iNs after transplantation in the postnatal cerebral cortex. Altogether, our data indicate that the origin of the astroglial population and transcription factors used for reprogramming, as well as the region of integration, affect the fate of iNs.Tese Reprogramming of distinct astroglial populations into specific neuronal subtypes in vitro and in vivo(Universidade Federal do Rio Grande do Norte, 2016-02-29) Chouchane, Malek; Costa, Marcos Romualdo; ; http://lattes.cnpq.br/6118493598074445; ; http://lattes.cnpq.br/0265428458441728; Pereira, Cecilia Hedin; ; http://lattes.cnpq.br/9205085846499207; Leão, Emelie Katarina Svahn; ; http://lattes.cnpq.br/1279823352935722; Reis, Ricardo Augusto de Melo; ; http://lattes.cnpq.br/6046165866539973; Souza, Sandro José de; ; http://lattes.cnpq.br/8479967495464590Recently, the field of cellular reprogramming has been revolutionized by works showing the potential to directly lineage-reprogram somatic cells into neurons upon overexpression of specific transcription factors. This technique offers a promising strategy to study the molecular mechanisms of neuronal specification, identify potential therapeutic targets for neurological diseases and eventually repair the central nervous system damaged by neurological conditions. Notably, studies with cortical astroglia revealed the high potential of these cells to reprogram into neurons using a single neuronal transcription factor. However, it remains unknown whether astroglia isolated from different regions of the central nervous system have the same neurogenic potential and generate induced neurons (iN) with similar phenotypes. Similarly, little is known about the fate that iNs could adopt after transplantation in the brain of host animals. In this study we compare the potential to reprogram astroglial cells isolated from the postnatal cerebral cortex and cerebellum into iNs both in vitro and in vivo using the proneural transcription factors Neurogenin-2 (Neurog2) and Achaete scute homolog-1 (Ascl1). Our results indicate cerebellar astroglia can be reprogrammed into induced neurons (iNs) with similar efficiencies to cerebral cortex astroglia. Notably however, while iNs in vitro adopt fates reminiscent of cortical or cerebellar neurons depending on the astroglial population used for reprogramming, in situ, after transplantation in the postnatal and adult mouse brain, iNs adopt fates compatible with the region of integration. Thus, our data suggest that the origin of the astroglial population used for lineage-reprogramming affects the fate of iNs in vitro, but this imprinting can be overridden by environmental cues after grafting.