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first analyzed expression of TrkC, a gene downregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7A and 7B). The level of expression of TrkC was indistinguishable from wild-type in DRG neurons of Er81EWS-Pea3/− and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7A, 7C, and 7D). Moreover, PV was not expressed in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure S5) but was expressed by proprioceptive afferents in both wild-type and Er81EWS-Pea3/− embryos (see Figures 1 and S5) [14]. We also found several genes that were ectopically upregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7). Calretinin and Calbindin, two different calcium-binding proteins expressed by subpopulations of DRG neurons in wild-type, Er81EWS-Pea3/−, and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7E, 7G, and 7H; data not shown) [31,32], were induced in more than 95% of all DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figures 7F and S5). These findings suggest that DRG neurons in TauEWS-Pea3/+ Isl1Cre/+ embryos fail to differentiate to a normal fate and instead acquire an aberrant identity distinct from any subpopulation of wild-type DRG neurons. Finally, to assess whether EWS-Pea3 expressed precociously acts exclusively cell-autonomously or whether it may also influence neighboring DRG neurons, we activated expression of EWS-Pea3 using Hb9Cre mice [33]. Due to a transient and rostro-caudally graded expression of Hb9 at neural plate stages, very few DRG neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination in TauEWS-Pea3/+ Hb9Cre/+ and TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Nevertheless, downregulation of Trk receptor expression or upregulation of Calretinin is restricted exclusively to neurons that have undergone recombination and cannot be observed in TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Together, these results and the findings obtained from in vitro culture experiments (see Figures 4 and 5) demonstrate that precocious or isochronic expression of EWS-Pea3 in the same neurons leads to significantly different cell-autonomous cellular responses with respect to gene expression, neuronal survival, and neurite outgrowth (Figure 9)."}

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first analyzed expression of TrkC, a gene downregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7A and 7B). The level of expression of TrkC was indistinguishable from wild-type in DRG neurons of Er81EWS-Pea3/− and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7A, 7C, and 7D). Moreover, PV was not expressed in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure S5) but was expressed by proprioceptive afferents in both wild-type and Er81EWS-Pea3/− embryos (see Figures 1 and S5) [14]. We also found several genes that were ectopically upregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7). Calretinin and Calbindin, two different calcium-binding proteins expressed by subpopulations of DRG neurons in wild-type, Er81EWS-Pea3/−, and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7E, 7G, and 7H; data not shown) [31,32], were induced in more than 95% of all DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figures 7F and S5). These findings suggest that DRG neurons in TauEWS-Pea3/+ Isl1Cre/+ embryos fail to differentiate to a normal fate and instead acquire an aberrant identity distinct from any subpopulation of wild-type DRG neurons. Finally, to assess whether EWS-Pea3 expressed precociously acts exclusively cell-autonomously or whether it may also influence neighboring DRG neurons, we activated expression of EWS-Pea3 using Hb9Cre mice [33]. Due to a transient and rostro-caudally graded expression of Hb9 at neural plate stages, very few DRG neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination in TauEWS-Pea3/+ Hb9Cre/+ and TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Nevertheless, downregulation of Trk receptor expression or upregulation of Calretinin is restricted exclusively to neurons that have undergone recombination and cannot be observed in TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Together, these results and the findings obtained from in vitro culture experiments (see Figures 4 and 5) demonstrate that precocious or isochronic expression of EWS-Pea3 in the same neurons leads to significantly different cell-autonomous cellular responses with respect to gene expression, neuronal survival, and neurite outgrowth (Figure 9)."}

{"project":"2_test","denotations":[{"id":"15836427-10850491-84719644","span":{"begin":498,"end":500},"obj":"10850491"},{"id":"15836427-2081815-84719645","span":{"begin":840,"end":842},"obj":"2081815"},{"id":"15836427-7812779-84719646","span":{"begin":843,"end":845},"obj":"7812779"},{"id":"15836427-11395002-84719647","span":{"begin":1373,"end":1375},"obj":"11395002"},{"id":"T86888","span":{"begin":498,"end":500},"obj":"10850491"},{"id":"T13726","span":{"begin":840,"end":842},"obj":"2081815"},{"id":"T49503","span":{"begin":843,"end":845},"obj":"7812779"},{"id":"T58140","span":{"begin":1373,"end":1375},"obj":"11395002"}],"text":"We first analyzed expression of TrkC, a gene downregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7A and 7B). The level of expression of TrkC was indistinguishable from wild-type in DRG neurons of Er81EWS-Pea3/− and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7A, 7C, and 7D). Moreover, PV was not expressed in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure S5) but was expressed by proprioceptive afferents in both wild-type and Er81EWS-Pea3/− embryos (see Figures 1 and S5) [14]. We also found several genes that were ectopically upregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7). Calretinin and Calbindin, two different calcium-binding proteins expressed by subpopulations of DRG neurons in wild-type, Er81EWS-Pea3/−, and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7E, 7G, and 7H; data not shown) [31,32], were induced in more than 95% of all DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figures 7F and S5). These findings suggest that DRG neurons in TauEWS-Pea3/+ Isl1Cre/+ embryos fail to differentiate to a normal fate and instead acquire an aberrant identity distinct from any subpopulation of wild-type DRG neurons. Finally, to assess whether EWS-Pea3 expressed precociously acts exclusively cell-autonomously or whether it may also influence neighboring DRG neurons, we activated expression of EWS-Pea3 using Hb9Cre mice [33]. Due to a transient and rostro-caudally graded expression of Hb9 at neural plate stages, very few DRG neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination in TauEWS-Pea3/+ Hb9Cre/+ and TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Nevertheless, downregulation of Trk receptor expression or upregulation of Calretinin is restricted exclusively to neurons that have undergone recombination and cannot be observed in TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Together, these results and the findings obtained from in vitro culture experiments (see Figures 4 and 5) demonstrate that precocious or isochronic expression of EWS-Pea3 in the same neurons leads to significantly different cell-autonomous cellular responses with respect to gene expression, neuronal survival, and neurite outgrowth (Figure 9)."}

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first analyzed expression of TrkC, a gene downregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7A and 7B). The level of expression of TrkC was indistinguishable from wild-type in DRG neurons of Er81EWS-Pea3/− and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7A, 7C, and 7D). Moreover, PV was not expressed in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure S5) but was expressed by proprioceptive afferents in both wild-type and Er81EWS-Pea3/− embryos (see Figures 1 and S5) [14]. We also found several genes that were ectopically upregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7). Calretinin and Calbindin, two different calcium-binding proteins expressed by subpopulations of DRG neurons in wild-type, Er81EWS-Pea3/−, and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7E, 7G, and 7H; data not shown) [31,32], were induced in more than 95% of all DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figures 7F and S5). These findings suggest that DRG neurons in TauEWS-Pea3/+ Isl1Cre/+ embryos fail to differentiate to a normal fate and instead acquire an aberrant identity distinct from any subpopulation of wild-type DRG neurons. Finally, to assess whether EWS-Pea3 expressed precociously acts exclusively cell-autonomously or whether it may also influence neighboring DRG neurons, we activated expression of EWS-Pea3 using Hb9Cre mice [33]. Due to a transient and rostro-caudally graded expression of Hb9 at neural plate stages, very few DRG neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination in TauEWS-Pea3/+ Hb9Cre/+ and TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Nevertheless, downregulation of Trk receptor expression or upregulation of Calretinin is restricted exclusively to neurons that have undergone recombination and cannot be observed in TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Together, these results and the findings obtained from in vitro culture experiments (see Figures 4 and 5) demonstrate that precocious or isochronic expression of EWS-Pea3 in the same neurons leads to significantly different cell-autonomous cellular responses with respect to gene expression, neuronal survival, and neurite outgrowth (Figure 9)."}

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first analyzed expression of TrkC, a gene downregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7A and 7B). The level of expression of TrkC was indistinguishable from wild-type in DRG neurons of Er81EWS-Pea3/− and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7A, 7C, and 7D). Moreover, PV was not expressed in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure S5) but was expressed by proprioceptive afferents in both wild-type and Er81EWS-Pea3/− embryos (see Figures 1 and S5) [14]. We also found several genes that were ectopically upregulated in DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figure 7). Calretinin and Calbindin, two different calcium-binding proteins expressed by subpopulations of DRG neurons in wild-type, Er81EWS-Pea3/−, and TauEWS-Pea3/+ PVCre/+ embryos (Figure 7E, 7G, and 7H; data not shown) [31,32], were induced in more than 95% of all DRG neurons of TauEWS-Pea3/+ Isl1Cre/+ embryos (Figures 7F and S5). These findings suggest that DRG neurons in TauEWS-Pea3/+ Isl1Cre/+ embryos fail to differentiate to a normal fate and instead acquire an aberrant identity distinct from any subpopulation of wild-type DRG neurons. Finally, to assess whether EWS-Pea3 expressed precociously acts exclusively cell-autonomously or whether it may also influence neighboring DRG neurons, we activated expression of EWS-Pea3 using Hb9Cre mice [33]. Due to a transient and rostro-caudally graded expression of Hb9 at neural plate stages, very few DRG neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination in TauEWS-Pea3/+ Hb9Cre/+ and TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Nevertheless, downregulation of Trk receptor expression or upregulation of Calretinin is restricted exclusively to neurons that have undergone recombination and cannot be observed in TaumGFP/+ Hb9Cre/+ embryos (Figure 8). Together, these results and the findings obtained from in vitro culture experiments (see Figures 4 and 5) demonstrate that precocious or isochronic expression of EWS-Pea3 in the same neurons leads to significantly different cell-autonomous cellular responses with respect to gene expression, neuronal survival, and neurite outgrowth (Figure 9)."}