c-Myb Is Required for Neural Progenitor Cell Proliferation and Maintenance of the Neural Stem Cell Niche in Adult Brain

Malaterre, Jordane; Mantamadiotis, Theo; Dworkin, Sebastian; Lightowler, Sally; Yang, Qing; Ransome, Mark I.; Turnley, Ann M.; Nichols, Nancy R.; Emambokus, Nikla; Frampton, Jon; Ramsay, Robert G.

doi:10.1634/stemcells.2007-0293

Cited by 83 publications

(72 citation statements)

References 54 publications

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“…Foxj1 and c-Myb are known to be key transcription factors controlling RGC differentiation towards the ependymal cell lineage (Jacquet et al, 2009;Malaterre et al, 2008). To gain insight into the molecular pathway by which Mcidas and GemC1 regulate ependymal cell generation we examined the expression of Foxj1 and c-Myb following deletion or overexpression of Mcidas and GemC1.…”

Section: Mcidas and Gemc1 Promote The Generation Of Ependymal Cells Tmentioning

confidence: 99%

“…It has been shown that Foxj1 and c-Myb regulate the differentiation of RGCs towards the ependymal cell lineage and maintain their identity (Jacquet et al, 2009;Malaterre et al, 2008), and that Six3 expression is crucial for the loss of radial glial characteristics of the differentiating ependymal cells (Lavado and Oliver, 2011). Ependymal cells contain in their apical surface multiple motile cilia and reside in a single cell layer facing the lateral ventricles (Doetsch et al, 1997), forming rosettelike structures surrounding a type B1 NSC (Mirzadeh et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

et al. 2015

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Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which is mutated in human mucociliary clearance disorder, and GemC1 (Gmnc or Lynkeas), previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cell generation in the mouse brain. Overexpression and knockdown experiments show that Mcidas and GemC1 are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells. Furthermore, we show that GemC1 and Mcidas operate in hierarchical order, upstream of Foxj1 and c-Myb transcription factors, which are known regulators of ependymal cell generation, and that Notch signaling inhibits GemC1 and Mcidas function. Our results suggest that Mcidas and GemC1 are key players in the generation of multiciliated ependymal cells of the adult neurogenic niche.

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Section: Mcidas and Gemc1 Promote The Generation Of Ependymal Cells Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

et al. 2015

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“…In fact, there are some indications that A-Myb and c-Myb may have a role in the mouse olfactory system. A-myb is expressed in the olfactory epithelium, while c-myb mutant mice have smaller olfactory bulbs (Trauth et al 1994;Malaterre et al 2008).…”

Section: Evolutionary Conservation and Odor Receptor Gene Expressionmentioning

confidence: 99%

Epigenetic regulation of olfactory receptor gene expression by the Myb–MuvB/dREAM complex

et al. 2012

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In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb-MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO 2 ) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/ Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO 2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map.

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“…Knockout mice have been generated for 7 of the 8 genes with neuronal enhancer activity, but a conditional brain-specific knockout has only been described for c-myb, which like Scl was found to be critical for neuronal development. 52 Known target genes of Scl in more mature erythroid and megakaryocyte cells such as Gata1, 53 Lmo2, 54 ␣-and ␤-globin, 20,55 as well as NF-E2 promoter, 56 respectively, were not bound by Scl in the HPC-7 cell line. We also did not observe binding to the Runx3 promoter, which previously showed low-level Scl binding in fetal liver and no binding in E8.5 yolk sac, 18 suggesting potential binding of Scl within subpopulations of hematopoietic progenitor cells.…”

mentioning

confidence: 94%

The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development

Wilson

Miranda‐Saavedra

Kinston

et al. 2009

Blood

111

125

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The basic helix-loop-helix transcription factor Scl/Tal1 controls the development and subsequent differentiation of hematopoietic stem cells (HSCs). However, because few Scl target genes have been validated to date, the underlying mechanisms have remained largely unknown. In this study, we have used ChIP-Seq technology (coupling chromatin immunoprecipitation with deep sequencing) to generate a genome-wide catalog of Scl-binding events in a stem/progenitor cell line, followed by validation using primary fetal IntroductionHematopoiesis has long served as a model system for adult stem cells, with many paradigms of stem cell biology first being established as a result of studying hematopoietic stem cells (HSCs). A large body of work over the past 25 years has established that transcription factors (TFs) play critical roles during the specification, maintenance, and/or differentiation of HSCs. However, the underlying mechanisms have remained largely obscure because of a lack of comprehensive data on target genes, as well as very limited information on the way key TFs interact to form the regulatory networks that control blood stem cell development and subsequent behavior.The basic helix-loop-helix (bHLH) TF Scl (also known as Tal1) is required for the specification of HSCs as well as their subsequent differentiation into erythroid and megakaryocytic lineages. 1,2 Sclnull embryos do not survive beyond embryonic day (E) 9.5 due to a complete absence of hematopoiesis, 3,4 a more striking phenotype than seen with other important regulators of early hematopoiesis such as Runx1 or Gata2. [5][6][7] Moreover, together with its paralogue Lyl1, Scl was recently shown to be essential for the survival of adult HSCs, thus emphasizing critical functions for Scl at multiple stages of hematopoietic ontogeny. 8 In addition to its pleiotropic roles in hematopoiesis, Scl is also required for vascular and central nervous system development. [9][10][11] Within the blood system, Scl is thought to be a key component of the regulatory networks controlling the specification and subsequent differentiation of HSCs. 12,13 Studies on the transcriptional regulation of the murine Scl gene identified Ets and Gata factors as well as an autoregulatory loop as key upstream inputs. [14][15][16] However, to fully understand how Scl functions within hematopoietic regulatory networks, comprehensive information on downstream target genes will also be required. Scl has been found to regulate a handful of genes, including Gata1, 17 Runx1, 18 c-kit, 19 and ␣-globin 20 in different hematopoietic lineages. However, to date, no systematic genome-scale approach has been taken to interrogate Scl target genes at early developmental time points in which Scl function is critical.Together with bHLH class I proteins, such as E47, Scl binds DNA as a heterodimer to the so-called E-box sequence motif CANNTG. In addition to its bHLH DNA-binding partners, Scl can interact with various proteins, including the lim-only protein Lmo2 and Gata factors Gata1/Gata2 in multimeric ...

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c-Myb Is Required for Neural Progenitor Cell Proliferation and Maintenance of the Neural Stem Cell Niche in Adult Brain

Cited by 83 publications

References 54 publications

Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

Epigenetic regulation of olfactory receptor gene expression by the Myb–MuvB/dREAM complex

The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development

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