Ets-1 Regulates Radial Glia Formation During Vertebrate Embryogenesis

Kiyota, Tomomi; Kato, Akira; Kato, Yoichi

doi:10.4161/org.3.2.5171

Cited by 19 publications

(22 citation statements)

References 69 publications

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“…The ETS family of genes is evolutionarily conserved [42,43,46,47] and formed by transcriptional regulators involved in various aspects of development, differentiation, hormone responses and tumorgenesis [4,48–55]. Our genome wide survey of ETS transcription factors present in Nematostella revealed the presence of 12 members of this gene family (Fig S1).…”

Section: Discussionmentioning

confidence: 96%

A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning

Amiel

Johnston

Chock

et al. 2017

Developmental Biology

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Germ layer formation and axial patterning are biological processes that are tightly linked during embryonic development of most metazoans. In addition to canonical WNT, it has been proposed that ERK-MAPK signaling is involved in specifying oral as well as aboral territories in cnidarians. However, the effector and the molecular mechanism underlying latter phenomenon is unknown. By screening for potential effectors of ERK-MAPK signaling in both domains, we identified a member of the ETS family of transcription factors, Nverg that is bi-polarily expressed prior to gastrulation. We further describe the crucial role of NvERG for gastrulation, endomesoderm as well as apical domain formation. The molecular characterization of the obtained NvERG knock-down phenotype using previously described as well as novel potential downstream targets, provides evidence that a single transcription factor, NvERG, simultaneously controls expression of two different sets of downstream targets, leading to two different embryonic gene regulatory networks (GRNs) in opposite poles of the developing embryo. We also highlight the molecular interaction of cWNT and MEK/ERK/ERG signaling that provides novel insight into the embryonic axial organization of Nematostella, and show a cWNT repressive role of MEK/ERK/ERG signaling in segregating the endomesoderm in two sub-domains, while a common input of both pathways is required for proper apical domain formation. Taking together, we build the first blueprint for a global cnidarian embryonic GRN that is the foundation for additional gene specific studies addressing the evolution of embryonic and larval development.

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Section: Discussionmentioning

confidence: 96%

A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning

Amiel

Johnston

Chock

et al. 2017

Developmental Biology

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“…Strikingly, we identify a new miR-219 target, Etv5, during OPC differentiation. Etv5 is a member of the Ets family of transcription factors that are necessary for gliogenesis in Drosophila , Xenopus , and mice (Kiyota et al, 2007; Klaes et al, 1994; Li et al, 2012). Here, we showed that downregulation of Etv5 enhances OL differentiation, whereas Etv5 overexpression repressed OPC differentiation in vitro, suggesting that Etv5 is an inhibitor of OL differentiation.…”

Section: Discussionmentioning

confidence: 99%

miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS

et al. 2017

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SUMMARY A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice. Integrated transcriptome profiling and biotin-affinity miRNA pull-down approaches reveal stage-specific miR-219 targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune encephalomyelitis, principal animal models of multiple sclerosis. Together, our findings identify context-specific miRNA-regulated checkpoints that control myelinogenesis and a therapeutic role for miR-219 in CNS myelin repair.

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“…Indeed a recent study has demonstrated an important role for a FGF-Rolled ( Drosophila MAPK)-Pointed signaling cascade in inducing glia differentiation in the Drosophila eye (Franzdottir et al, 2009). In Xenopus, both loss and gain of function studies demonstrated that RAS-MAPK signaling acts through Xenopus Ets-1 to regulate radial glia development (Kiyota et al, 2007). In the mammalian PNS, Erm has been implicated in glial cell fate decisions of neural crest progenitors (Hagedorn et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

MEK Is a Key Regulator of Gliogenesis in the Developing Brain

Newbern

et al. 2012

Neuron

151

176

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We have defined functions of MEK in regulating gliogenesis in developing cerebral cortex using loss and gain of function mouse genetics. Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found that the key cytokine regulated gliogenic pathway is attenuated. Further, the Ets transcription family member Etv5/Erm is strongly regulated by MEK and Erm overexpression can rescue the gliogenic potential of Mek deleted progenitors. Remarkably, Mek1/2 deleted mice surviving postnatally exhibit cortices almost devoid of astrocytes and oligodendroglia and exhibit neurodegeneration. Conversely, expression of constitutively active MEK1 leads to a major increase in numbers of astrocytes in the adult brain. We conclude that MEK is essential for acquisition of gliogenic competence by radial progenitors, and that levels of MEK activity regulate gliogenesis in the developing cortex.

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Ets-1 Regulates Radial Glia Formation During Vertebrate Embryogenesis

Cited by 19 publications

References 69 publications

A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning

A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning

miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS

MEK Is a Key Regulator of Gliogenesis in the Developing Brain

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