Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6

Hack, Michael A.; Sugimori, Michiya; Lundberg, Cecilia; Nakafuku, Masato; Götz, Magdalena

doi:10.1016/j.mcn.2003.12.012

Cited by 252 publications

(279 citation statements)

References 75 publications

Supporting

Mentioning

243

Contrasting

Unclassified

Order By: Relevance

“…This concept was supported by data in rodents showing that transcriptional regulators of embryonic precursors were also expressed by adult SVZa progenitors: Pax6 and Olig2 (Hack et al, 2004), Emx2 (Galli et al, 2002), Dlx2 (Doetsch et al, 2002), and Sox2 (Ferri et al, 2004;Komitova and Eriksson, 2004). We first report expression of developmentally-regulated transcription factors at protein level by SVZa progenitor cells of adult primate brain.…”

Section: Discussionsupporting

confidence: 57%

“…Expression of several of these developmental signals has been shown in adult rodent SVZa precursors, including paired-box (Pax) 6 (Heins et al, 2002;Hack et al, 2004), empty spiracles-homeobox (Emx) 2 (Galli et al, 2002), distalless-homeobox (Dlx) 2 (Doetsch et al, 2002), sex determining region Y-box (Sox) 2 (Ferri et al, 2004;Komitova and Eriksson, 2004), and oligodendrocyte lineage gene (Olig) 2 (Hack et al, 2004). At present, however, little is known of transcription factor expression by progenitor cells in adult primate SVZa.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Tonchev¹,

Yamashima²,

Sawamoto³

2006

Neuroscience

View full text Add to dashboard Cite

Abstract-The anterior subventricular zone of the adult mammalian brain contains progenitor cells which are upregulated after cerebral ischemia. We have previously reported that while a part of the progenitors residing in adult monkey anterior subventricular zone travels to the olfactory bulb, many of these cells sustain location in the anterior subventricular zone for months after injury, exhibiting a phenotype of either neural or neuronal precursors. Here we show that ischemia increased the numbers of anterior subventricular zone progenitor cells expressing developmentally regulated transcription factors including Pax6 (paired-box 6), Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3), Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains. Analysis of transcription factor protein expression by sustained neural or neuronal precursors in anterior subventricular zone revealed that these two cell types were positive for characteristic sets of transcription factors. The proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were mainly expressed by neuronal precursors. Further, differences between monkeys and non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and Dlx2. Our results suggest that a complex network of developmental signals might be involved in the specification of primate progenitor cells.

show abstract

Section: Discussionsupporting

confidence: 57%

mentioning

confidence: 99%

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Tonchev¹,

Yamashima²,

Sawamoto³

2006

Neuroscience

View full text Add to dashboard Cite

show abstract

“…30 It has, however, also been shown that Mash1 can rapidly be degraded during BMP-mediated astroglial differentiation of forebrain progenitors. 31 We, therefore, assessed whether nuclear Mash1 expression was affected by the CNTF-mediated astrocytic differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Most importantly, Itoh et al 17 focused at roles for p57Kip2 and other CKIs in the dorsal telencephalon and neocortex, whereas in this study, we used an in vitro system of telencephalic neural progenitors that include both dorsal and ventral progenitors and is known to be 'ventralized' in character by the FGF2-mediated expansion of the stem cell cultures. 30 As the expression of CKIs and neurogenic factors such as bHLH transcription factors show spatiotemporal variations during telencephalic development, conditional gene deletion strategies will be required to elucidate these questions in more detail.…”

Section: Discussionmentioning

confidence: 99%

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

et al. 2009

View full text Add to dashboard Cite

Mammalian central nervous system (CNS) development is a highly organized process involving the precise and coordinated timing of cell-cycle exit, differentiation, survival, and migration. These events require proper expression of pro-neuronal genes but also repression of alternative cell fates and restriction of cell-type-specific gene expression. Here, we show that the cyclindependent kinase (CDK) inhibitor p57Kip2 interacted with pro-neuronal basic helix-loop-helix (bHLH) factors such as Mash1, NeuroD, and Nex/Math2. Increased levels of p57Kip2 inhibited Mash1 transcriptional activity independently of CDK interactions and acted as a direct repressor in transcriptional assays. Proliferating telencephalic neural progenitors co-expressed basal levels of Mash1 and p57Kip2, and endogenous p57Kip2 accumulated transiently in the nuclei of neural stem cells (NSCs) during early stages of astrocyte differentiation mediated by ciliary neurotrophic factor (CNTF), independent of cell-cycle exit and at times when Mash1 expression was still prominent. In accordance with these observations, gain-and loss-of-function studies showed that p57Kip2 repressed neuronal differentiation after mitogen withdrawal, but exerted little or no effect on CNTFmediated astroglial differentiation of NSCs. Our data suggest a novel role for p57Kip2 as a context-dependent repressor of neurogenic transcription factors and telencephalic neuronal differentiation. The development of the mammalian central nervous system (CNS) critically relies on a tight coordination among cell proliferation, survival, migration, and differentiation. 1,2 Proper neuronal differentiation does not only require pro-neuronal genes but also regulated repression of other cell fates, such as glial differentiation. 2 Thus, early neural progenitors preferentially differentiate into neurons and do not respond properly to astrocyte-inducing cytokines, at least in part due to DNA methylation of astrocyte-characteristic genes such as glial fibrillary acidic protein (GFAP). 3,4 In line with these observations, it has been shown that loss of the DNA methyl transferase DNMT1 results in hypomethylation and precocious onset of astrocytic genes at the expense of neurogenesis in early neural precursors. 5 In later progenitors, astrocytic genes become demethylated. 3,4 Transcriptional repression of astrocytic genes and thus the correct numbers of progenitors and neurons at these late events, instead depends on other factors such as the Notch-regulated transcription factor CSL/RBP-Jk and the co-repressors N-CoR and SMRT. 6,7 In addition, neurogenic members of the basic helix-loop-helix (bHLH) family of transcription factors, such as Mash1 and Neurogenin (Ngn) 2, interferes with astrocyte differentiation in multipotent neural progenitors at least in part by sequestering the coactivators CBP/p300 required for astrocyte differentiation. 8 Less is understood regarding a corresponding repression of neuronal differentiation during glial differentiation. Hes transcription factors repress neurogenic ...

show abstract

“…and Gotz, 2003;Hack et al, 2004). Olig2 inhibits the differentiation of neural progenitors into astrocytes (Fukuda et al, 2004;Muroyama et al, 2005) and its expression is downregulated in vitro and in vivo in mature astrocytes (Fukuda et al, 2004;Marshall et al, 2005).…”

Section: Tgfa Dedifferentiates Astrocytesmentioning

confidence: 99%

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

et al. 2006

View full text Add to dashboard Cite

Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6

Cited by 252 publications

References 75 publications

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

Contact Info

Product

Resources

About