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null mutants at birth (P0)\nVestibular ganglia are smaller in Brn3c null mutants (Fig. 1b) than in control littermates (Fig. 1a), but larger than in BDNF or trkB null mutants of the same age [13,15]. The reduction in apparent size of the vestibular ganglia is in agreement with quantitative data published previously [3,13]. These data suggest a loss of 80–85% of vestibular sensory neurons in BDNF and trkB null mutants [13] and of 77% of vestibular sensory neurons in P4 Brn3c null mutants [3]. Thus, the size reduction in the vestibular sensory ganglion could be compatible with a loss of BDNF production in the immature hair cells.\nFigure 1 Size variations of vestibular ganglia in control and mutant littermates labeled with DiI. In newborn animals, the vestibular ganglion shows a dramatic reduction in Brn3c null mutants (b) compared to control littermates (a). Abbreviations for this and other figures: AC, anterior crista; ggl, ganglion; c, spiral capillary; Genic. ggl., geniculate ganglion; GER, greater epithelial ridge; HC, horizontal crista; HaC, vestibular hair cell; IHC, inner hair cell; iHC, immature hair cell; IGSB, intraganglionic spiral bundle; OHC, outer hair cell; PC, posterior crista; S, saccule; SG, spiral ganglion; TM, tectorial membrane; U, utricle; VCN, ventral cochlear nucleus; VG, vestibular ganglion. Bar indicates 1000 μm. However, the Brn3c null mutants show only a reduced density of afferent and efferent fibers to all vestibular sensory epithelia. There is no specific loss of all afferent and efferent innervation to the canal crista (Fig. 2a), a hallmark of both BDNF and trkB null mutations [13,15]. In fact, the reduction of fibers seems to be rather uniform throughout a given sensory epithelium with the crista innervation being qualitatively no more reduced than the innervation of the utricle and saccule. No loss in specific areas, comparable to that in BDNF null mutant mice, is apparent in the saccule or utricle of Brn3c null mice. Similar patterns of innervation are obtained using acteylated tubulin immunocytochemistry (Fig. 2b).\nFigure 2 Innervation of Brn3c null and control ears are shown for newborn mice. There is no specific loss of fibers to any vestibular endorgan, as visualized by DiI labeling (a) or acetylated tubulin immunoreactivity (b). No major differences in pattern of projection through radial fibers are found in the cochlea of Brn3c null mutants (d,f) as compared to control littermates (c). Note, however, the lack of orderly fiber outgrowth to the outer hair cells (c, d). Efferent fibers to the ear show a well developed intraganglionic spiral bundle (IGSB) with no detectable differences compared to controls (e). Bar indicates 100 μm. Consistent with the finding of Xiang et al. [3] of only a 29% loss of spiral sensory neurons at P4, our data show little difference in the pattern of innervation of the cochlea in P0 Brn3c null mutants (Fig. 2c,2d). No selective loss of spiral neurons is observed in Brn3c null mutants in the basal turn, a feature of either NT-3 or trkC loss [6,9,14]. Likewise, the innervation of the apex (Fig. 2f) shows no detectable abnormality in overall pattern of innervation compared to control animals (data not shown), an indication that BDNF could be expressed in the apex [6]. In addition, the pattern of efferent innervation shows no deviation from normal either (Fig. 2e), whereas they show the same pattern of loss as afferent fibers in neurotrophin null mutants [16]. These data suggest that the spiral sensory neurons develop qualitatively normal at least until P0 and therefore allow normal pathfinding of efferents. Most interestingly, there is no increase in radial fiber spacing in the apex, a specific problem of BDNF null mutants [6,13].\nHowever, there is one qualitative difference not recognized in any single neurotrophin null mutant. Afferents reach all three rows of outer hair cells in the basal turn of control wildtype littermates (Fig. 2c), but both afferent and efferent outgrowth is disorganized to outer hair cells in Brn3c null mutants (Fig. 2d) and does not show any clear organization into three distinct longitudinal fiber bundles paralleling the three rows in the outer hair cell region. These data suggest that fiber organization in the outer hair cell region is partly disrupted in Brn3c null mutant."}

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The reduction in apparent size of the vestibular ganglia is in agreement with quantitative data published previously [3,13]. These data suggest a loss of 80–85% of vestibular sensory neurons in BDNF and trkB null mutants [13] and of 77% of vestibular sensory neurons in P4 Brn3c null mutants [3]. Thus, the size reduction in the vestibular sensory ganglion could be compatible with a loss of BDNF production in the immature hair cells.\nFigure 1 Size variations of vestibular ganglia in control and mutant littermates labeled with DiI. In newborn animals, the vestibular ganglion shows a dramatic reduction in Brn3c null mutants (b) compared to control littermates (a). Abbreviations for this and other figures: AC, anterior crista; ggl, ganglion; c, spiral capillary; Genic. ggl., geniculate ganglion; GER, greater epithelial ridge; HC, horizontal crista; HaC, vestibular hair cell; IHC, inner hair cell; iHC, immature hair cell; IGSB, intraganglionic spiral bundle; OHC, outer hair cell; PC, posterior crista; S, saccule; SG, spiral ganglion; TM, tectorial membrane; U, utricle; VCN, ventral cochlear nucleus; VG, vestibular ganglion. Bar indicates 1000 μm. However, the Brn3c null mutants show only a reduced density of afferent and efferent fibers to all vestibular sensory epithelia. There is no specific loss of all afferent and efferent innervation to the canal crista (Fig. 2a), a hallmark of both BDNF and trkB null mutations [13,15]. In fact, the reduction of fibers seems to be rather uniform throughout a given sensory epithelium with the crista innervation being qualitatively no more reduced than the innervation of the utricle and saccule. No loss in specific areas, comparable to that in BDNF null mutant mice, is apparent in the saccule or utricle of Brn3c null mice. Similar patterns of innervation are obtained using acteylated tubulin immunocytochemistry (Fig. 2b).\nFigure 2 Innervation of Brn3c null and control ears are shown for newborn mice. There is no specific loss of fibers to any vestibular endorgan, as visualized by DiI labeling (a) or acetylated tubulin immunoreactivity (b). No major differences in pattern of projection through radial fibers are found in the cochlea of Brn3c null mutants (d,f) as compared to control littermates (c). Note, however, the lack of orderly fiber outgrowth to the outer hair cells (c, d). Efferent fibers to the ear show a well developed intraganglionic spiral bundle (IGSB) with no detectable differences compared to controls (e). Bar indicates 100 μm. Consistent with the finding of Xiang et al. [3] of only a 29% loss of spiral sensory neurons at P4, our data show little difference in the pattern of innervation of the cochlea in P0 Brn3c null mutants (Fig. 2c,2d). No selective loss of spiral neurons is observed in Brn3c null mutants in the basal turn, a feature of either NT-3 or trkC loss [6,9,14]. Likewise, the innervation of the apex (Fig. 2f) shows no detectable abnormality in overall pattern of innervation compared to control animals (data not shown), an indication that BDNF could be expressed in the apex [6]. In addition, the pattern of efferent innervation shows no deviation from normal either (Fig. 2e), whereas they show the same pattern of loss as afferent fibers in neurotrophin null mutants [16]. These data suggest that the spiral sensory neurons develop qualitatively normal at least until P0 and therefore allow normal pathfinding of efferents. Most interestingly, there is no increase in radial fiber spacing in the apex, a specific problem of BDNF null mutants [6,13].\nHowever, there is one qualitative difference not recognized in any single neurotrophin null mutant. Afferents reach all three rows of outer hair cells in the basal turn of control wildtype littermates (Fig. 2c), but both afferent and efferent outgrowth is disorganized to outer hair cells in Brn3c null mutants (Fig. 2d) and does not show any clear organization into three distinct longitudinal fiber bundles paralleling the three rows in the outer hair cell region. These data suggest that fiber organization in the outer hair cell region is partly disrupted in Brn3c null mutant."}

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SLOT","subj":"T8569","obj":"T8570"},{"id":"R5599","pred":"NULL SLOT","subj":"T8570","obj":"T8569"},{"id":"R5600","pred":"NULL SLOT","subj":"T8575","obj":"T8576"},{"id":"R5601","pred":"NULL SLOT","subj":"T8576","obj":"T8575"},{"id":"R997","pred":"_lexicallyChainedTo","subj":"T1795","obj":"T1794"},{"id":"R998","pred":"_lexicallyChainedTo","subj":"T1820","obj":"T1819"}],"text":"Brn3c null mutants at birth (P0)\nVestibular ganglia are smaller in Brn3c null mutants (Fig. 1b) than in control littermates (Fig. 1a), but larger than in BDNF or trkB null mutants of the same age [13,15]. The reduction in apparent size of the vestibular ganglia is in agreement with quantitative data published previously [3,13]. These data suggest a loss of 80–85% of vestibular sensory neurons in BDNF and trkB null mutants [13] and of 77% of vestibular sensory neurons in P4 Brn3c null mutants [3]. Thus, the size reduction in the vestibular sensory ganglion could be compatible with a loss of BDNF production in the immature hair cells.\nFigure 1 Size variations of vestibular ganglia in control and mutant littermates labeled with DiI. In newborn animals, the vestibular ganglion shows a dramatic reduction in Brn3c null mutants (b) compared to control littermates (a). Abbreviations for this and other figures: AC, anterior crista; ggl, ganglion; c, spiral capillary; Genic. ggl., geniculate ganglion; GER, greater epithelial ridge; HC, horizontal crista; HaC, vestibular hair cell; IHC, inner hair cell; iHC, immature hair cell; IGSB, intraganglionic spiral bundle; OHC, outer hair cell; PC, posterior crista; S, saccule; SG, spiral ganglion; TM, tectorial membrane; U, utricle; VCN, ventral cochlear nucleus; VG, vestibular ganglion. Bar indicates 1000 μm. However, the Brn3c null mutants show only a reduced density of afferent and efferent fibers to all vestibular sensory epithelia. There is no specific loss of all afferent and efferent innervation to the canal crista (Fig. 2a), a hallmark of both BDNF and trkB null mutations [13,15]. In fact, the reduction of fibers seems to be rather uniform throughout a given sensory epithelium with the crista innervation being qualitatively no more reduced than the innervation of the utricle and saccule. No loss in specific areas, comparable to that in BDNF null mutant mice, is apparent in the saccule or utricle of Brn3c null mice. Similar patterns of innervation are obtained using acteylated tubulin immunocytochemistry (Fig. 2b).\nFigure 2 Innervation of Brn3c null and control ears are shown for newborn mice. There is no specific loss of fibers to any vestibular endorgan, as visualized by DiI labeling (a) or acetylated tubulin immunoreactivity (b). No major differences in pattern of projection through radial fibers are found in the cochlea of Brn3c null mutants (d,f) as compared to control littermates (c). Note, however, the lack of orderly fiber outgrowth to the outer hair cells (c, d). Efferent fibers to the ear show a well developed intraganglionic spiral bundle (IGSB) with no detectable differences compared to controls (e). Bar indicates 100 μm. Consistent with the finding of Xiang et al. [3] of only a 29% loss of spiral sensory neurons at P4, our data show little difference in the pattern of innervation of the cochlea in P0 Brn3c null mutants (Fig. 2c,2d). No selective loss of spiral neurons is observed in Brn3c null mutants in the basal turn, a feature of either NT-3 or trkC loss [6,9,14]. Likewise, the innervation of the apex (Fig. 2f) shows no detectable abnormality in overall pattern of innervation compared to control animals (data not shown), an indication that BDNF could be expressed in the apex [6]. In addition, the pattern of efferent innervation shows no deviation from normal either (Fig. 2e), whereas they show the same pattern of loss as afferent fibers in neurotrophin null mutants [16]. These data suggest that the spiral sensory neurons develop qualitatively normal at least until P0 and therefore allow normal pathfinding of efferents. Most interestingly, there is no increase in radial fiber spacing in the apex, a specific problem of BDNF null mutants [6,13].\nHowever, there is one qualitative difference not recognized in any single neurotrophin null mutant. Afferents reach all three rows of outer hair cells in the basal turn of control wildtype littermates (Fig. 2c), but both afferent and efferent outgrowth is disorganized to outer hair cells in Brn3c null mutants (Fig. 2d) and does not show any clear organization into three distinct longitudinal fiber bundles paralleling the three rows in the outer hair cell region. These data suggest that fiber organization in the outer hair cell region is partly disrupted in Brn3c null mutant."}