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first assessed the influence of EWS-Pea3 expression in early post-mitotic DRG neurons on the establishment of afferent projections into the spinal cord using the TaumGFP/+ allele or a Thy1-promoter-driven synaptophysin green fluorescent protein (spGFP) with an expression profile restricted to DRG sensory neurons at embryonic day (E) 13.5 (Thy1spGFP; [25]) (Figure 3). In contrast to wild-type proprioceptive afferent projections (Figure 3A–3C), GFP+ sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos failed to invade the spinal cord and instead were found in an extreme lateral position at the dorsal root entry zone, a phenotype observed at least up to E18.5 (Figure 3A–3C and 3G–3I; data not shown). We next visualized the path of sensory afferent projections towards the dorsal root entry zone in TauEWS-Pea3/+ Isl1Cre/+ embryos by injecting fluorescently labeled dextran into an individual DRG (L3; n = 3; Figure 3M–3Q). Sensory afferents in E13.5 wild-type embryos bifurcated at their lateral spinal entry point, and projected rostrally and caudally over six or more segmental levels while gradually approaching the midline (Figure 3M). Sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos also bifurcated at the entry point, although approximately 5% of afferent fibers continued to grow towards the midline (Figure 3O and 3Q). While rostro-caudal projections were present in TauEWS-Pea3/+ Isl1Cre/+ embryos, afferent fibers failed to approach the midline at distal segments and continued to occupy an extreme lateral position (Figure 3O), consistent with the analysis of transverse sections."}

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In contrast to wild-type proprioceptive afferent projections (Figure 3A–3C), GFP+ sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos failed to invade the spinal cord and instead were found in an extreme lateral position at the dorsal root entry zone, a phenotype observed at least up to E18.5 (Figure 3A–3C and 3G–3I; data not shown). We next visualized the path of sensory afferent projections towards the dorsal root entry zone in TauEWS-Pea3/+ Isl1Cre/+ embryos by injecting fluorescently labeled dextran into an individual DRG (L3; n = 3; Figure 3M–3Q). Sensory afferents in E13.5 wild-type embryos bifurcated at their lateral spinal entry point, and projected rostrally and caudally over six or more segmental levels while gradually approaching the midline (Figure 3M). Sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos also bifurcated at the entry point, although approximately 5% of afferent fibers continued to grow towards the midline (Figure 3O and 3Q). While rostro-caudal projections were present in TauEWS-Pea3/+ Isl1Cre/+ embryos, afferent fibers failed to approach the midline at distal segments and continued to occupy an extreme lateral position (Figure 3O), consistent with the analysis of transverse sections."}

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In contrast to wild-type proprioceptive afferent projections (Figure 3A–3C), GFP+ sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos failed to invade the spinal cord and instead were found in an extreme lateral position at the dorsal root entry zone, a phenotype observed at least up to E18.5 (Figure 3A–3C and 3G–3I; data not shown). We next visualized the path of sensory afferent projections towards the dorsal root entry zone in TauEWS-Pea3/+ Isl1Cre/+ embryos by injecting fluorescently labeled dextran into an individual DRG (L3; n = 3; Figure 3M–3Q). Sensory afferents in E13.5 wild-type embryos bifurcated at their lateral spinal entry point, and projected rostrally and caudally over six or more segmental levels while gradually approaching the midline (Figure 3M). Sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos also bifurcated at the entry point, although approximately 5% of afferent fibers continued to grow towards the midline (Figure 3O and 3Q). While rostro-caudal projections were present in TauEWS-Pea3/+ Isl1Cre/+ embryos, afferent fibers failed to approach the midline at distal segments and continued to occupy an extreme lateral position (Figure 3O), consistent with the analysis of transverse sections."}

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In contrast to wild-type proprioceptive afferent projections (Figure 3A–3C), GFP+ sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos failed to invade the spinal cord and instead were found in an extreme lateral position at the dorsal root entry zone, a phenotype observed at least up to E18.5 (Figure 3A–3C and 3G–3I; data not shown). We next visualized the path of sensory afferent projections towards the dorsal root entry zone in TauEWS-Pea3/+ Isl1Cre/+ embryos by injecting fluorescently labeled dextran into an individual DRG (L3; n = 3; Figure 3M–3Q). Sensory afferents in E13.5 wild-type embryos bifurcated at their lateral spinal entry point, and projected rostrally and caudally over six or more segmental levels while gradually approaching the midline (Figure 3M). Sensory afferents in TauEWS-Pea3/+ Isl1Cre/+ embryos also bifurcated at the entry point, although approximately 5% of afferent fibers continued to grow towards the midline (Figure 3O and 3Q). While rostro-caudal projections were present in TauEWS-Pea3/+ Isl1Cre/+ embryos, afferent fibers failed to approach the midline at distal segments and continued to occupy an extreme lateral position (Figure 3O), consistent with the analysis of transverse sections."}