Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

Messina, Graziella; Biressi, Stefano; Monteverde, Stefania; Magli, Alessandro; Cassano, Marco; Perani, Laura; Roncaglia, Elena; Tagliafico, Enrico; Starnes, Linda M.; Campbell, Christine; Grossi, Milena; Goldhamer, David J.; Gronostajski, Richard M.; Cossu, Giulio

doi:10.1016/j.cell.2010.01.027

Cited by 189 publications

(248 citation statements)

References 41 publications

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“…NFI transcription factors can activate and repress gene transcription depending on the gene and cellular context (Chang et al, 2013;Gronostajski, 2000;Messina et al, 2010). NFIB influences stem cell maintenance and differentiation in several tissues including in the SVZ as part of a cross-regulatory network together with Pax6/Brg1 (Chang et al, 2013;Ninkovic et al, 2013 (Chang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

et al. 2016

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SUMMARYMulti-lineage neuronal, astrocytic and oligodendrocytic potential is considered a neural stem cell (NSC) trait. However, hippocampal NSCs generate neurons and astrocytes but not oligodendrocytes in vivo and how this is regulated is unknown. Here we show that the RNAseIII Drosha is an intrinsic regulator of stem cell maintenance and differentiation in the adult mouse hippocampus. Inactivation of Drosha results in exhaustion of the NSC pool, premature arrest of neurogenesis, and induction of oligodendrocyte fate commitment. Drosha silences Nuclear Factor IB (NFIB) in hippocampal NSCs by targeting a double-stranded hairpin in the NFIB mRNA, thereby repressing its expression in a Dicer and miRNA-independent manner. We show that NFIB is required and sufficient for oligodendrocyte fate and knockdown of NFIB rescues neurogenesis by Drosha-deficient hippocampal NSCs. Our findings reveal a novel mechanism for stem cell maintenance and oligodendrocyte fate restriction in the adult hippocampus.3

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Section: Discussionmentioning

confidence: 99%

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

et al. 2016

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“…6A; Supplemental Fig. S5A-D; Messina et al 2010). EdU incorporation and flow cytometry analysis showed that in proliferation conditions, Nfix shRNA-expressing and control cells proliferated at the same rate, suggesting that Nfix does not play a major role in NS cell proliferation (Supplemental Fig.…”

Section: Nfix Is Both Required and Sufficient To Induce Aspects Of Qumentioning

confidence: 99%

“…shRNA knockdown of Nfix Lentiviral particles encoding a control or Nfix-specific shRNA construct and a puromycin resistance cassette (Messina et al 2010) were generated in 293T cells according to standard procedures. Proliferating NS cells were transduced with the lentiviruses, and, 24 h later, 2 mg/mL puromycin was added to select for shRNA-expressing cells.…”

Section: Ns Cellsmentioning

confidence: 99%

Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

Martynoga¹,

et al. 2013

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The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, the transcriptional mechanisms involved are mostly unknown, largely due to lack of a cell culture model. In this study, we first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular and transcriptional characteristics of quiescent cells. We then use epigenomic profiling to identify enhancers associated with the quiescent NS cell state. Motif enrichment analysis of these enhancers predicts a major role for the nuclear factor one (NFI) family in the gene regulatory network controlling NS cell quiescence. Interestingly, we found that the family member NFIX is robustly induced when NS cells enter quiescence. Using genome-wide location analysis and overexpression and silencing experiments, we demonstrate that NFIX has a major role in the induction of quiescence in cultured NSCs. Transcript profiling of NS cells overexpressing or silenced for Nfix and the phenotypic analysis of the hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by regulating the interactions of NSCs with their microenvironment.

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“…TGF-b family members inhibit muscle differentiation and growth following receptor binding and the initiation of specific intracellular signals by Smad2 and Smad3 proteins, whereas BMP signaling through Smad1, Smad5 and Smad8 is a positive regulator of muscle growth (Gardner et al, 2011;Sartori et al, 2009;Sartori et al, 2013;Winbanks et al, 2013). Recent data have also implicated specific members of the nuclear factor I (NFI/Nfi) family of transcription factors in muscle morphogenesis (Gronostajski, 2000), Nfia being responsible for the induction of embryonic muscle genes, whereas Nfix activates fetal genes (Messina et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration

Deák¹,

Mátés²,

Korpos³

et al. 2014

Development

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BSTRACTHere, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog, explaining the retarded cell cycle exit and myoblast differentiation. Rescue of Matn2 expression restored differentiation and the expression of p21 and of the myogenic genes. TGF-b1 inhibited myogenic differentiation at least in part by repressing Matn2 expression, which inhibited the onset of a positive-feedback loop whereby Matn2 and Nfix activate the expression of one another and activate myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2 2/2 relative to wild-type mice. The expression levels of Trf3 and myogenic genes were robustly reduced in Matn2 2/2 fetal limbs and in differentiating primary myoblast cultures, establishing Matn2 as a key modulator of the regulatory cascade that initiates terminal myogenic differentiation. Our data thus identify Matn2 as a crucial component of a genetic switch that modulates the onset of tissue repair.

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Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

Cited by 189 publications

References 41 publications

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration

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