Glial cells generate neurons: the role of the transcription factor Pax6

Heins, Nico; Malatesta, Paolo; Cecconi, Francesco; Nakafuku, Masato; Tucker, Kerry L.; Hack, Michael A.; Chapouton, Prisca; Barde, Yves‐Alain; Götz, Magdalena

doi:10.1038/nn828

Cited by 698 publications

(671 citation statements)

References 48 publications

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“…Recently, it was demonstrated that Pax6 mutants have reduced neurogenesis. Retrovirally mediated Pax6 expression instruct radial glia cells to differentiate to neurons, indicating the dual role of radial glial cell, namely, contribution to neurogenesis in addition to the support of migrating neurons during development (Heins et al, 2002). Whether this pertains to adult cells is not clear.…”

Section: Stem Cells In the Cnsmentioning

confidence: 99%

Mechanism of stem cells in the central nervous system

Johansson

2003

Journal Cellular Physiology

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Injury to the central nervous system (CNS) can result in severe functional impairment. The brain and spinal cord, which constitute the CNS, have been viewed for decades as having a very limited capacity for regeneration. However, over the last several years, the body of evidence supporting the concept of regeneration and continuous renewal of neurons in specific regions of the CNS has increased. This evidence has significantly altered our perception of the CNS and has offered new hope for possible cell therapy strategies to repair lost function. Transplantation of stem cells or the recruitment of endogenous stem cells to repair specific regions of the brain or spinal cord is the next exciting research challenge. However, our understanding of the existing stem cell pool in the adult CNS remains limited. This review will discuss the identification and characterization of CNS stem cells in the adult brain and spinal cord.

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Section: Stem Cells In the Cnsmentioning

confidence: 99%

Mechanism of stem cells in the central nervous system

Johansson

2003

Journal Cellular Physiology

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“…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%

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

Tonchev¹,

Yamashima²,

Sawamoto³

2006

Neuroscience

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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.

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“…toggle switch – (Fig. 1, blue box) that has been shown to determine cellular commitment and provides stability to transcriptional programs mediating binary cell fate choices 83, 84, 85, 86, 87. This has been observed in other cellular systems, such as the common myeloid progenitor (mutual inhibition of Gata1 and PU.1 ) 88 and embryonic stem cells (mutual inhibition of Oct4 and Cdx2 ) 89.…”

Section: Specific Gene Regulatory Network Circuits Regulate the Balanmentioning

confidence: 90%

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

Angarica

Sol

2016

BioEssays

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Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self‐renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation‐specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine.

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Glial cells generate neurons: the role of the transcription factor Pax6

Cited by 698 publications

References 48 publications

Mechanism of stem cells in the central nervous system

Mechanism of stem cells in the central nervous system

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

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

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