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situ hybridization confirms neonatal neurotrophin expression\nWe processed four ears of P0 and P8 Brn3c null and control littermates for expression of BDNF and NT-3 using the riboprobes previously described [7]. We did not analyze neurotrophin expression in 6-month old animals as neurotrophins are downregulated in neonates [20] and no expression can be found even in normal animals [4]. In the canal cristae we expected, and found, only a BDNF signal. This signal was very strong over hair cells of the P0 control animals (Fig. 8b). In contrast, only a faint signal was detected in the Brn3c null mutant (Fig. 8a) and the few silver grains were located predominantly over the area of the immature hair cells. The BDNF signal in the utricle was clearly centered on the hair cells in the control animal but some aggregation of silver grains appeared also in the Brn3c null mutants (data not shown).\nFigure 8 The expression of BDNF and NT-3 mRNA is shown in the P0 vestibular sensory epithelia. Silver grains are false colored as red to enhance visibility against the grey Nissl-stained background. Canal cristae contain only BDNF (a,b), but gravistatic endorgans, such as saccule and utricle, contain both BDNF and NT-3 (c-f). Note the prominent BDNF expression in the hair cell region (HaC) of control canal (b) and saccule (d) and low levels of expression in the Brn3c null mice (a,c) over immature hair cells (iHC). The NT-3 expression is much more diffuse in both control and Brn3c mutant littermates. Bar indicates 100 μm. In the saccule, we directly compared the BDNF (Fig. 8c,8d) and NT-3 signal (Fig. 8e,8f) of the Brn3c null mutant (Fig. 8c,8e) and control littermates (Fig. 8d,8f). A strong BDNF signal was found over the hair cells of control animals and an occasional immature hair cell also showed a BDNF signal in the Brn3c null mutants. The NT-3 signal was more diffuse in both the control and the Brn3c null littermates but showed some slightly above background signal in the area of the sensory epithelium even in the Brn3c null mutant.\nIn the cochlea, the BDNF signal was very weak in the base in both the control (Fig. 9b) and the Brn3c null littermates (Fig. 9a). However, there was a surprisingly strong NT-3 signal over the organ of Corti in the apex of Brn3c null littermates (Fig. 9c) that closely matched the signal found in the control littermates (Fig. 9d). The NT-3 signal in the area of the cochlea that corresponds to the IHC's persisted at least until P8 in the apex of Brn3c null mice (Fig. 9e,9f).\nFigure 9 BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c null and control littermates. Note the limited expression of BDNF in the basal turn of both wildtype and mutant littermates (a,b) and the much stronger expression of NT-3 in the apex over the region of the inner hair cells in both wildtype and control littermates (c,d). NT-3 expression persists at least until P8 in the apex of Brn3c null mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T10325","span":{"begin":3048,"end":3055},"obj":"NCBITaxon:33208"},{"id":"T10324","span":{"begin":3020,"end":3036},"obj":"CL:0000589"},{"id":"T10323","span":{"begin":2969,"end":2973},"obj":"NCBITaxon:10088"},{"id":"T10322","span":{"begin":2958,"end":2963},"obj":"PR:000013043"},{"id":"T10321","span":{"begin":2905,"end":2915},"obj":"GO:0010467"},{"id":"T10320","span":{"begin":2900,"end":2904},"obj":"PR:000011459"},{"id":"T10319","span":{"begin":2835,"end":2851},"obj":"CL:0000589"},{"id":"T10318","span":{"begin":2795,"end":2799},"obj":"PR:000011459"},{"id":"T10317","span":{"begin":2781,"end":2791},"obj":"GO:0010467"},{"id":"T10316","span":{"begin":2690,"end":2694},"obj":"PR:000004716"},{"id":"T10315","span":{"begin":2676,"end":2686},"obj":"GO:0010467"},{"id":"T10314","span":{"begin":2623,"end":2628},"obj":"PR:000013043"},{"id":"T10313","span":{"begin":2590,"end":2597},"obj":"UBERON:0001844"},{"id":"T10312","span":{"begin":2563,"end":2573},"obj":"GO:0010467"},{"id":"T10311","span":{"begin":2553,"end":2557},"obj":"PR:000011459"},{"id":"T10310","span":{"begin":2544,"end":2548},"obj":"PR:000004716"},{"id":"T10117","span":{"begin":1483,"end":1488},"obj":"PR:000013043"},{"id":"T10116","span":{"begin":1431,"end":1441},"obj":"GO:0010467"},{"id":"T10115","span":{"begin":1426,"end":1430},"obj":"PR:000011459"},{"id":"T10114","span":{"begin":1404,"end":1414},"obj":"CL:0000855"},{"id":"T10113","span":{"begin":1379,"end":1383},"obj":"NCBITaxon:10088"},{"id":"T10112","span":{"begin":1368,"end":1373},"obj":"PR:000013043"},{"id":"T10111","span":{"begin":1350,"end":1360},"obj":"GO:0010467"},{"id":"T10110","span":{"begin":1320,"end":1327},"obj":"UBERON:0001854"},{"id":"T10109","span":{"begin":1306,"end":1311},"obj":"UBERON:0000025"},{"id":"T10108","span":{"begin":1272,"end":1281},"obj":"CL:0000855"},{"id":"T10107","span":{"begin":1254,"end":1264},"obj":"GO:0010467"},{"id":"T10106","span":{"begin":1249,"end":1253},"obj":"PR:000004716"},{"id":"T10105","span":{"begin":1218,"end":1222},"obj":"PR:000011459"},{"id":"T10104","span":{"begin":1209,"end":1213},"obj":"PR:000004716"},{"id":"T10103","span":{"begin":1187,"end":1194},"obj":"UBERON:0001853"},{"id":"T10102","span":{"begin":1175,"end":1182},"obj":"UBERON:0001854"},{"id":"T10101","span":{"begin":1128,"end":1132},"obj":"PR:000004716"},{"id":"T10100","span":{"begin":1107,"end":1114},"obj":"UBERON:0004721"},{"id":"T10099","span":{"begin":1101,"end":1106},"obj":"UBERON:0000025"},{"id":"T10098","span":{"begin":967,"end":995},"obj":"UBERON:0006932"},{"id":"T10097","span":{"begin":938,"end":942},"obj":"PR:000011459"},{"id":"T10096","span":{"begin":929,"end":933},"obj":"PR:000004716"},{"id":"T10095","span":{"begin":915,"end":925},"obj":"GO:0010467"},{"id":"T4162","span":{"begin":2515,"end":2519},"obj":"NCBITaxon:10088"},{"id":"T4161","span":{"begin":2504,"end":2509},"obj":"PR:000013043"},{"id":"T4160","span":{"begin":2455,"end":2460},"obj":"CL:0000589"},{"id":"T4159","span":{"begin":2423,"end":2430},"obj":"UBERON:0001844"},{"id":"T4158","span":{"begin":2392,"end":2396},"obj":"PR:000011459"},{"id":"T4157","span":{"begin":2279,"end":2284},"obj":"PR:000013043"},{"id":"T4156","span":{"begin":2249,"end":2263},"obj":"UBERON:0002227"},{"id":"T4155","span":{"begin":2228,"end":2232},"obj":"PR:000011459"},{"id":"T4154","span":{"begin":2153,"end":2158},"obj":"PR:000013043"},{"id":"T4153","span":{"begin":2077,"end":2081},"obj":"PR:000004716"},{"id":"T4152","span":{"begin":2064,"end":2071},"obj":"UBERON:0001844"},{"id":"T4151","span":{"begin":2038,"end":2043},"obj":"PR:000013043"},{"id":"T4150","span":{"begin":2007,"end":2025},"obj":"UBERON:0006934"},{"id":"T4149","span":{"begin":1916,"end":1921},"obj":"PR:000013043"},{"id":"T4148","span":{"begin":1859,"end":1863},"obj":"PR:000011459"},{"id":"T4147","span":{"begin":1835,"end":1840},"obj":"PR:000013043"},{"id":"T4146","span":{"begin":1816,"end":1820},"obj":"PR:000004716"},{"id":"T4145","span":{"begin":1792,"end":1801},"obj":"CL:0000855"},{"id":"T4144","span":{"begin":1757,"end":1764},"obj":"NCBITaxon:33208"},{"id":"T4143","span":{"begin":1735,"end":1745},"obj":"CL:0000855"},{"id":"T4142","span":{"begin":1704,"end":1708},"obj":"PR:000004716"},{"id":"T4141","span":{"begin":1626,"end":1631},"obj":"PR:000013043"},{"id":"T4140","span":{"begin":1594,"end":1598},"obj":"PR:000011459"},{"id":"T4139","span":{"begin":1572,"end":1576},"obj":"PR:000004716"},{"id":"T4138","span":{"begin":1538,"end":1545},"obj":"UBERON:0001854"},{"id":"T4137","span":{"begin":864,"end":869},"obj":"PR:000013043"},{"id":"T4136","span":{"begin":798,"end":804},"obj":"NCBITaxon:33208"},{"id":"T4135","span":{"begin":772,"end":782},"obj":"CL:0000855"},{"id":"T4134","span":{"begin":736,"end":743},"obj":"UBERON:0001853"},{"id":"T4133","span":{"begin":717,"end":721},"obj":"PR:000004716"},{"id":"T4132","span":{"begin":701,"end":711},"obj":"CL:0000855"},{"id":"T4131","span":{"begin":590,"end":595},"obj":"PR:000013043"},{"id":"T4130","span":{"beg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situ hybridization confirms neonatal neurotrophin expression\nWe processed four ears of P0 and P8 Brn3c null and control littermates for expression of BDNF and NT-3 using the riboprobes previously described [7]. We did not analyze neurotrophin expression in 6-month old animals as neurotrophins are downregulated in neonates [20] and no expression can be found even in normal animals [4]. In the canal cristae we expected, and found, only a BDNF signal. This signal was very strong over hair cells of the P0 control animals (Fig. 8b). In contrast, only a faint signal was detected in the Brn3c null mutant (Fig. 8a) and the few silver grains were located predominantly over the area of the immature hair cells. The BDNF signal in the utricle was clearly centered on the hair cells in the control animal but some aggregation of silver grains appeared also in the Brn3c null mutants (data not shown).\nFigure 8 The expression of BDNF and NT-3 mRNA is shown in the P0 vestibular sensory epithelia. Silver grains are false colored as red to enhance visibility against the grey Nissl-stained background. Canal cristae contain only BDNF (a,b), but gravistatic endorgans, such as saccule and utricle, contain both BDNF and NT-3 (c-f). Note the prominent BDNF expression in the hair cell region (HaC) of control canal (b) and saccule (d) and low levels of expression in the Brn3c null mice (a,c) over immature hair cells (iHC). The NT-3 expression is much more diffuse in both control and Brn3c mutant littermates. Bar indicates 100 μm. In the saccule, we directly compared the BDNF (Fig. 8c,8d) and NT-3 signal (Fig. 8e,8f) of the Brn3c null mutant (Fig. 8c,8e) and control littermates (Fig. 8d,8f). A strong BDNF signal was found over the hair cells of control animals and an occasional immature hair cell also showed a BDNF signal in the Brn3c null mutants. The NT-3 signal was more diffuse in both the control and the Brn3c null littermates but showed some slightly above background signal in the area of the sensory epithelium even in the Brn3c null mutant.\nIn the cochlea, the BDNF signal was very weak in the base in both the control (Fig. 9b) and the Brn3c null littermates (Fig. 9a). However, there was a surprisingly strong NT-3 signal over the organ of Corti in the apex of Brn3c null littermates (Fig. 9c) that closely matched the signal found in the control littermates (Fig. 9d). The NT-3 signal in the area of the cochlea that corresponds to the IHC's persisted at least until P8 in the apex of Brn3c null mice (Fig. 9e,9f).\nFigure 9 BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c null and control littermates. Note the limited expression of BDNF in the basal turn of both wildtype and mutant littermates (a,b) and the much stronger expression of NT-3 in the apex over the region of the inner hair cells in both wildtype and control littermates (c,d). NT-3 expression persists at least until P8 in the apex of Brn3c null mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm."}

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situ hybridization confirms neonatal neurotrophin expression\nWe processed four ears of P0 and P8 Brn3c null and control littermates for expression of BDNF and NT-3 using the riboprobes previously described [7]. We did not analyze neurotrophin expression in 6-month old animals as neurotrophins are downregulated in neonates [20] and no expression can be found even in normal animals [4]. In the canal cristae we expected, and found, only a BDNF signal. This signal was very strong over hair cells of the P0 control animals (Fig. 8b). In contrast, only a faint signal was detected in the Brn3c null mutant (Fig. 8a) and the few silver grains were located predominantly over the area of the immature hair cells. The BDNF signal in the utricle was clearly centered on the hair cells in the control animal but some aggregation of silver grains appeared also in the Brn3c null mutants (data not shown).\nFigure 8 The expression of BDNF and NT-3 mRNA is shown in the P0 vestibular sensory epithelia. Silver grains are false colored as red to enhance visibility against the grey Nissl-stained background. Canal cristae contain only BDNF (a,b), but gravistatic endorgans, such as saccule and utricle, contain both BDNF and NT-3 (c-f). Note the prominent BDNF expression in the hair cell region (HaC) of control canal (b) and saccule (d) and low levels of expression in the Brn3c null mice (a,c) over immature hair cells (iHC). The NT-3 expression is much more diffuse in both control and Brn3c mutant littermates. Bar indicates 100 μm. In the saccule, we directly compared the BDNF (Fig. 8c,8d) and NT-3 signal (Fig. 8e,8f) of the Brn3c null mutant (Fig. 8c,8e) and control littermates (Fig. 8d,8f). A strong BDNF signal was found over the hair cells of control animals and an occasional immature hair cell also showed a BDNF signal in the Brn3c null mutants. The NT-3 signal was more diffuse in both the control and the Brn3c null littermates but showed some slightly above background signal in the area of the sensory epithelium even in the Brn3c null mutant.\nIn the cochlea, the BDNF signal was very weak in the base in both the control (Fig. 9b) and the Brn3c null littermates (Fig. 9a). However, there was a surprisingly strong NT-3 signal over the organ of Corti in the apex of Brn3c null littermates (Fig. 9c) that closely matched the signal found in the control littermates (Fig. 9d). The NT-3 signal in the area of the cochlea that corresponds to the IHC's persisted at least until P8 in the apex of Brn3c null mice (Fig. 9e,9f).\nFigure 9 BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c null and control littermates. Note the limited expression of BDNF in the basal turn of both wildtype and mutant littermates (a,b) and the much stronger expression of NT-3 in the apex over the region of the inner hair cells in both wildtype and control littermates (c,d). NT-3 expression persists at least until P8 in the apex of Brn3c null mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm."}