Fate specification in the adult brain – lessons for eliciting neurogenesis from glial cells

Ninkovic, Jovica; Götz, Magdalena

doi:10.1002/bies.201200108

Cited by 38 publications

(25 citation statements)

References 107 publications

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“…Indeed, transplantation of many neural stem cells into the adult brain parenchyma results in their conversion to gliogenesis, while they readily generate neurons in the developing brain (for review see (Ninkovic and Gotz, 2013)). Thus, neuroblasts face particular challenges in the adult brain, not to convert to gliogenesis.…”

Section: Discussionmentioning

confidence: 99%

The BAF Complex Interacts with Pax6 in Adult Neural Progenitors to Establish a Neurogenic Cross-Regulatory Transcriptional Network

Ninkovic

Steiner-Mezzadri

Jawerka³

et al. 2013

Cell Stem Cell

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196

203

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The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. Here we define the mechanisms of installing neurogenic fate by the transcription factor Pax6 acting together with the Brg1-containing BAF chromatin remodeling complex. We show that Pax6 physically interacts with Brg1-containing BAF complex and genetic deletion of either Pax6 or Brg1, in the neural stem cells in the adult mouse subependymal zone results in a strikingly similar fate conversion from neuronal progenitors to glia. The Pax6-BAF complex drives neurogenesis by directly activating transcription factors Sox11, Nfib and Pou3f4, which form a cross-regulatory network that maintains neurogenic fate downstream of the Pax6-BAF complex in neuroblasts. Our work identifies a novel concept of stratification in neural fate commitment with a strikingly specific role of the Pax6-BAF complex in initiating a cross-regulatory network essential for maintenance of the neurogenic lineage in the adult brain.

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Section: Discussionmentioning

confidence: 99%

The BAF Complex Interacts with Pax6 in Adult Neural Progenitors to Establish a Neurogenic Cross-Regulatory Transcriptional Network

Ninkovic

Steiner-Mezzadri

Jawerka³

et al. 2013

Cell Stem Cell

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196

203

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“…The homeostasis of NPCs in the striatum is a regulated process in which neurogenesis precedes astro-gliogenesis during development (Alvarez-Buylla et al, 2001; Ninkovic and Götz, 2013). However, contrary to the increase of astro-gliogenesis observed in Ikaros −/− mice (Martín-Ibáñez et al, 2010), we could not detect any effects on glial cells in He −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

et al. 2017

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Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G1/G0 phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, He−/− mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.

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“…We discuss the basic principles of cortical neurogenesis and their cell biological basis www.annualreviews.org • Cell Biology of Neurogenesis and then proceed to the stem and progenitor cell diversity involved in expanding the neocortex. Topics beyond the scope of this review include transcriptional regulation of neurogenesis in the developing neocortex, adult neurogenesis, neuronal migration and differentiation, and gliogenesis; here, the reader is referred to recent reviews (Cremisi 2013, Guerout et al 2014, Hippenmeyer 2014, Ninkovic & Götz 2013, Paridaen & Huttner 2014, Rowitch & Kriegstein 2010, Tuoc et al 2014.…”

Section: Stem and Progenitor Cellsmentioning

confidence: 99%

The Cell Biology of Neurogenesis: Toward an Understanding of the Development and Evolution of the Neocortex

Taverna

Götz

Huttner

2014

Annu. Rev. Cell Dev. Biol.

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659

768

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Neural stem and progenitor cells have a central role in the development and evolution of the mammalian neocortex. In this review, we first provide a set of criteria to classify the various types of cortical stem and progenitor cells. We then discuss the issue of cell polarity, as well as specific subcellular features of these cells that are relevant for their modes of division and daughter cell fate. In addition, cortical stem and progenitor cell behavior is placed into a tissue context, with consideration of extracellular signals and cell-cell interactions. Finally, the differences across species regarding cortical stem and progenitor cells are dissected to gain insight into key developmental and evolutionary mechanisms underlying neocortex expansion.

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Fate specification in the adult brain – lessons for eliciting neurogenesis from glial cells

Cited by 38 publications

References 107 publications

The BAF Complex Interacts with Pax6 in Adult Neural Progenitors to Establish a Neurogenic Cross-Regulatory Transcriptional Network

The BAF Complex Interacts with Pax6 in Adult Neural Progenitors to Establish a Neurogenic Cross-Regulatory Transcriptional Network

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

The Cell Biology of Neurogenesis: Toward an Understanding of the Development and Evolution of the Neocortex

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