Notch Intracellular Domain Deficiency in Nuclear Localization Activity Retains the Ability to Enhance Neural Stem Cell Character and Block Neurogenesis in Mammalian Brain Development

Jang, Jaeshin; Byun, Sung‐Hyun; Han, Dasol; Lee, Junsub; Kim, Ju‐Wan; Lee, Nayeon; Kim, Inhee; Park, Soo-Jeong; Ha, Soobong; Kwon, Mookwang; Ahn, Jyhyun; Chung, Woo‐Jae; Kweon, Dae-Hyuk; Cho, Jae Youl; Kim, Sun‐Young; Yoon, Keejung

doi:10.1089/scd.2014.0031

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Interestingly, we also noted that TRBP increased astrocyte production at the expense of neurogenesis under differentiating conditions in vitro (Fig. 1J,K); this is reminiscent of Notch effects in the embryonic central nervous system (Yoon and Gaiano, 2005;Jang et al, 2014).…”

Section: Resultsmentioning

confidence: 56%

TRBP maintains mammalian embryonic neural stem cell properties by enhancing the Notch signaling pathway as a novel transcriptional coactivator

et al. 2017

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Transactivation response element RNA-binding protein (TRBP) is known to play important roles in human immunodeficiency virus (HIV) replication and microRNA biogenesis. However, recent studies implicate TRBP in a variety of biological processes as a mediator for cross-talk between signal transduction pathways. Here, we provide the first evidence that TRBP is required for efficient neurosphere formation, and expression of neural stem cell markers and Notch target genes in primary neural progenitor cells in vitro. Consistent with this, introduction of TRBP into the mouse embryonic brain in utero increased the fraction of cells expressing Sox2 in the ventricular zone (VZ). We also show TRBP physically interacts with the Notch transcriptional coactivation complex through C promoter binding factor 1 (CBF1) and strengthens the association between the Notch intracellular domain (NICD) and CBF1, resulting in increased NICD recruitment to the promoter region of a Notch target gene. Our data indicate that TRBP is a novel transcriptional coactivator of the Notch signaling pathway playing an important role in neural stem cell regulation during mammalian brain development.

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Section: Resultsmentioning

confidence: 56%

TRBP maintains mammalian embryonic neural stem cell properties by enhancing the Notch signaling pathway as a novel transcriptional coactivator

et al. 2017

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“…Furthermore, the Notch/delta pathway was examined that is involved in the maintenance of the aNSPC compartment [ 43 ]. The proportion of cleaved Notch1 receptor (Notch intracellular domain, NICD) serves as an indicator of the activation of this pathway and was normalized with regard to the total amount of Notch1.…”

Section: Resultsmentioning

confidence: 99%

The extracellular matrix molecule tenascin-C modulates cell cycle progression and motility of adult neural stem/progenitor cells from the subependymal zone

Schaberg

Götz

Faissner

2022

Cell. Mol. Life Sci.

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Adult neurogenesis has been described in two canonical regions of the adult central nervous system (CNS) of rodents, the subgranular zone (SGZ) of the hippocampus and the subependymal zone (SEZ) of the lateral ventricles. The stem cell niche of the SEZ provides a privileged environment composed of a specialized extracellular matrix (ECM) that comprises the glycoproteins tenascin-C (Tnc) and laminin-1 (LN1). In the present study, we investigated the function of these ECM glycoproteins in the adult stem cell niche. Adult neural stem/progenitor cells (aNSPCs) of the SEZ were prepared from wild type (Tnc+/+) and Tnc knockout (Tnc−/−) mice and analyzed using molecular and cell biological approaches. A delayed maturation of aNSPCs in Tnc−/− tissue was reflected by a reduced capacity to form neurospheres in response to epidermal growth factor (EGF). To examine a potential influence of the ECM on cell proliferation, aNSPCs of both genotypes were studied by cell tracking using digital video microscopy. aNSPCs were cultivated on three different substrates, namely, poly-d-lysine (PDL) and PDL replenished with either LN1 or Tnc for up to 6 days in vitro. On each of the three substrates aNSPCs displayed lineage trees that could be investigated with regard to cell cycle length. The latter appeared reduced in Tnc−/− aNSPCs on PDL and LN1 substrates, less so on Tnc that seemed to compensate the absence of the ECM compound to some extent. Close inspection of the lineage trees revealed a subpopulation of late dividing aNSPCslate that engaged into cycling after a notable delay. aNSPCslate exhibited a clearly different morphology, with a larger cell body and conspicuous processes. aNSPCslate reiterated the reduction in cell cycle length on all substrates tested, which was not rescued on Tnc substrates. When the migratory activity of aNSPC-derived progeny was determined, Tnc−/− neuroblasts displayed significantly longer migration tracks. This was traced to an increased rate of migration episodes compared to the wild-type cells that rested for longer time periods. We conclude that Tnc intervenes in the proliferation of aNSPCs and modulates the motility of neuroblasts in the niche of the SEZ.

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“…Furthermore, the Notch/delta pathway was examined that is involved in the maintenance of the aNSPC compartment [37]. The proportion of cleaved Notch1 receptor (Notch intracellular domain, NICD) serves as an indicator of the activation of this pathway and was normalized with regard to the total amount of Notch1.…”

Section: Functional Analysis Of Anspc Progeny In Wildtype and Tnc-de Cient Culturesmentioning

confidence: 99%

Cell Tracking of Adult Neural Stem Cells From The Subependymal Zone In Vitro Reveals Cell Type-Specific Impacts On Cell Cycle Progression By The Extracellular Matrix Molecule Tenascin-C

Schaberg

Götz

Faissner

2021

Preprint

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Adult neurogenesis has been described in two canonical regions of the adult central nervous system (CNS) of rodents, the subgranular zone (SGZ) of the hippocampus and the subependymal zone (SEZ) of the lateral ventricles. The stem cell niche of the SEZ provides a privileged environment composed of a specialized extracellular matrix (ECM) that comprises the glycoproteins tenascin-C (Tnc) and laminin-1 (LN1). In the present study, we investigated the function of these ECM glycoproteins in the adult stem cell niche. Adult neural stem cells (aNSPCs) of the SEZ were prepared from wildtype (Tnc+/+) and Tnc knockout (Tnc-/-) mice and analyzed using molecular and cell biological approaches. A delayed maturation of aNSPCs in Tnc-/- tissue was reflected by a reduced capacity to form neurospheres in response to epidermal growth factor (EGF). In order to examine a potential influence of the ECM on cell proliferation, aNSPCs of both genotypes were studied by cell tracking using digital video microscopy. aNSPCs were cultivated on three different substrates, namely poly-D-Lysine (PDL) and PDL replenished with either LN1 or Tnc for up to six days in vitro. On each of the three substrates aNSPCs displayed lineage trees that could be investigated with regard to cell cycle length. The latter appeared reduced in Tnc-/- aNSPCs on PDL and LN1 substrates, less so on Tnc that seemed to compensate the absence of the ECM compound to some extent. Close inspection of the lineage trees revealed a subpopulation of late dividing aNSPCslate that engaged into cycling after a notable delay. aNSPCslate exhibited a clearly different morphology, with a larger cell body and conspicuous processes. aNSPCslate reiterated the reduction in cell cycle length on all substrates tested, which was not rescued on Tnc substrates. When the migratory activity of aNSPC-derived progeny was determined, Tnc-/- neuroblasts displayed significantly longer migration tracks. This was traced to an increased rate of migration episodes compared to the wildtype cells that rested for longer time periods. We conclude that Tnc intervenes in the proliferation of aNSPCs and modulates the motility of neuroblasts in the niche of the SEZ.

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Notch Intracellular Domain Deficiency in Nuclear Localization Activity Retains the Ability to Enhance Neural Stem Cell Character and Block Neurogenesis in Mammalian Brain Development

Cited by 9 publications

References 28 publications

TRBP maintains mammalian embryonic neural stem cell properties by enhancing the Notch signaling pathway as a novel transcriptional coactivator

TRBP maintains mammalian embryonic neural stem cell properties by enhancing the Notch signaling pathway as a novel transcriptional coactivator

The extracellular matrix molecule tenascin-C modulates cell cycle progression and motility of adult neural stem/progenitor cells from the subependymal zone

Cell Tracking of Adult Neural Stem Cells From The Subependymal Zone In Vitro Reveals Cell Type-Specific Impacts On Cell Cycle Progression By The Extracellular Matrix Molecule Tenascin-C

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