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findings are compatible with a model in which DRG neurons acquire their mature fate by sequential and temporally controlled addition of lineage-specific features (Figure 9). Target-derived factors act on predetermined neuronal lineages to switch their developmental programs to become compatible with processes such as target invasion and branching. Such a transition state in the acquisition of a defined neuronal fate would be accompanied by the induction of appropriate transcriptional programs through the expression of specific transcription factors. Mechanisms such as chromosomal remodeling that restrict or expand access to certain target genes [34] or activation by cofactors responsible for changing the action of particular transcription factors [35] could represent possible mechanisms by which the downstream transcriptional profile of a transcription factor could be temporally shifted towards the selection and control of distinct target genes. Interestingly, several ETS transcription factors are activated through release of autoinhibition via interaction with cofactors and/or via post-translational modifications [35,36,37]. The fusion of EWS with Pea3 could circumvent a need for activation through specific cofactors while still maintaining ETS site dependence, thus rendering EWS-Pea3 less sensitive to the cellular context than endogenous ETS transcription factors. Using this fusion protein, our experiments demonstrate a profound change in the action of ETS signaling at the level of transcriptional regulation within post-mitotic DRG neurons over time. Moreover, the observed transcriptional shift in ETS signaling is paired with the onset of appropriate regulation of neuronal subtype specification and establishment of axonal projections into the target area."}

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Target-derived factors act on predetermined neuronal lineages to switch their developmental programs to become compatible with processes such as target invasion and branching. Such a transition state in the acquisition of a defined neuronal fate would be accompanied by the induction of appropriate transcriptional programs through the expression of specific transcription factors. Mechanisms such as chromosomal remodeling that restrict or expand access to certain target genes [34] or activation by cofactors responsible for changing the action of particular transcription factors [35] could represent possible mechanisms by which the downstream transcriptional profile of a transcription factor could be temporally shifted towards the selection and control of distinct target genes. Interestingly, several ETS transcription factors are activated through release of autoinhibition via interaction with cofactors and/or via post-translational modifications [35,36,37]. The fusion of EWS with Pea3 could circumvent a need for activation through specific cofactors while still maintaining ETS site dependence, thus rendering EWS-Pea3 less sensitive to the cellular context than endogenous ETS transcription factors. Using this fusion protein, our experiments demonstrate a profound change in the action of ETS signaling at the level of transcriptional regulation within post-mitotic DRG neurons over time. Moreover, the observed transcriptional shift in ETS signaling is paired with the onset of appropriate regulation of neuronal subtype specification and establishment of axonal projections into the target area."}

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findings are compatible with a model in which DRG neurons acquire their mature fate by sequential and temporally controlled addition of lineage-specific features (Figure 9). Target-derived factors act on predetermined neuronal lineages to switch their developmental programs to become compatible with processes such as target invasion and branching. Such a transition state in the acquisition of a defined neuronal fate would be accompanied by the induction of appropriate transcriptional programs through the expression of specific transcription factors. Mechanisms such as chromosomal remodeling that restrict or expand access to certain target genes [34] or activation by cofactors responsible for changing the action of particular transcription factors [35] could represent possible mechanisms by which the downstream transcriptional profile of a transcription factor could be temporally shifted towards the selection and control of distinct target genes. Interestingly, several ETS transcription factors are activated through release of autoinhibition via interaction with cofactors and/or via post-translational modifications [35,36,37]. The fusion of EWS with Pea3 could circumvent a need for activation through specific cofactors while still maintaining ETS site dependence, thus rendering EWS-Pea3 less sensitive to the cellular context than endogenous ETS transcription factors. Using this fusion protein, our experiments demonstrate a profound change in the action of ETS signaling at the level of transcriptional regulation within post-mitotic DRG neurons over time. Moreover, the observed transcriptional shift in ETS signaling is paired with the onset of appropriate regulation of neuronal subtype specification and establishment of axonal projections into the target area."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T10509","span":{"begin":50,"end":53},"obj":"UBERON:0000044"},{"id":"T10510","span":{"begin":54,"end":61},"obj":"CL:0000540"},{"id":"T10511","span":{"begin":117,"end":127},"obj":"GO:0065007"},{"id":"T10512","span":{"begin":222,"end":230},"obj":"CL:0000540"},{"id":"T10513","span":{"begin":410,"end":418},"obj":"CL:0000540"},{"id":"T10514","span":{"begin":514,"end":524},"obj":"GO:0010467"},{"id":"T10515","span":{"begin":651,"end":656},"obj":"SO:0000704"},{"id":"T10516","span":{"begin":679,"end":688},"obj":"CHEBI:23357"},{"id":"T10517","span":{"begin":930,"end":937},"obj":"GO:0065007"},{"id":"T10518","span":{"begin":957,"end":962},"obj":"SO:0000704"},{"id":"T10519","span":{"begin":1082,"end":1091},"obj":"CHEBI:23357"},{"id":"T10520","span":{"begin":1108,"end":1121},"obj":"GO:0006412"},{"id":"T10521","span":{"begin":1162,"end":1165},"obj":"PR:000007243"},{"id":"T10522","span":{"begin":1171,"end":1175},"obj":"PR:000007227"},{"id":"T10523","span":{"begin":1232,"end":1241},"obj":"CHEBI:23357"},{"id":"T10524","span":{"begin":1302,"end":1305},"obj":"PR:000007243"},{"id":"T10525","span":{"begin":1306,"end":1310},"obj":"PR:000007227"},{"id":"T10526","span":{"begin":1529,"end":1539},"obj":"GO:0065007"},{"id":"T10527","span":{"begin":1552,"end":1559},"obj":"GO:0007067"},{"id":"T10528","span":{"begin":1560,"end":1563},"obj":"UBERON:0000044"},{"id":"T10529","span":{"begin":1564,"end":1571},"obj":"CL:0000540"},{"id":"T10530","span":{"begin":1685,"end":1695},"obj":"GO:0065007"},{"id":"T10531","span":{"begin":1699,"end":1707},"obj":"CL:0000540"},{"id":"T10532","span":{"begin":1751,"end":1769},"obj":"GO:0030424"}],"text":"Our findings are compatible with a model in which DRG neurons acquire their mature fate by sequential and temporally controlled addition of lineage-specific features (Figure 9). Target-derived factors act on predetermined neuronal lineages to switch their developmental programs to become compatible with processes such as target invasion and branching. Such a transition state in the acquisition of a defined neuronal fate would be accompanied by the induction of appropriate transcriptional programs through the expression of specific transcription factors. Mechanisms such as chromosomal remodeling that restrict or expand access to certain target genes [34] or activation by cofactors responsible for changing the action of particular transcription factors [35] could represent possible mechanisms by which the downstream transcriptional profile of a transcription factor could be temporally shifted towards the selection and control of distinct target genes. Interestingly, several ETS transcription factors are activated through release of autoinhibition via interaction with cofactors and/or via post-translational modifications [35,36,37]. The fusion of EWS with Pea3 could circumvent a need for activation through specific cofactors while still maintaining ETS site dependence, thus rendering EWS-Pea3 less sensitive to the cellular context than endogenous ETS transcription factors. Using this fusion protein, our experiments demonstrate a profound change in the action of ETS signaling at the level of transcriptional regulation within post-mitotic DRG neurons over time. Moreover, the observed transcriptional shift in ETS signaling is paired with the onset of appropriate regulation of neuronal subtype specification and establishment of axonal projections into the target area."}