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Brn3c mutant mice show long-term, incomplete retention of some afferent inner ear innervation.

Xiang M, Maklad A, Pirvola U, Fritzsch B - BMC Neurosci (2003)

Bottom Line: At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin mutations.At postnatal day 7/8 (P7/8), innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base.Despite more severe loss of hair cells (1% compared to 20%), the cochlea retains many more sensory neurons (46% compared to 15%) than vestibular epithelia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Advanced Biotechnology and Medicine, Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. xiang@cabm.rutgers.edu

ABSTRACT

Background: Ears of Brn3c mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates. This partial development of hair cells could lead to enough neurotrophin expression to sustain sensory neurons through embryonic development. We have therefore investigated in these mutants the patterns of innervation and of expression of known neurotrophins.

Results: At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin mutations. At postnatal day 7/8 (P7/8), innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base. Around 20% of immature hair cells exist in the mutant vestibular sensory epithelia. Despite more severe loss of hair cells (1% compared to 20%), the cochlea retains many more sensory neurons (46% compared to 15%) than vestibular epithelia. Even 6 months old mutant mice have some fibers to all vestibular sensory epithelia and many more to the cochlear apex which lacks MyoVIIa positive hair cells. Topologically organized central cochlea projections exist at least until P8, suggesting that functional hair cells are not required to establish such projections.

Conclusion: The limited expression of neurotrophins in the cochlea of Brn3c mice suffices to support many sensory neurons, particularly in the cochlea, until birth. The molecular nature of the long term survival of apical spiral neurons remains unclear.

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BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c  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  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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Figure 9: BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c 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 mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm.

Mentions: In the cochlea, the BDNF signal was very weak in the base in both the control (Fig. 9b) and the Brn3c littermates (Fig. 9a). However, there was a surprisingly strong NT-3 signal over the organ of Corti in the apex of Brn3c 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 mice (Fig. 9e,9f).


Brn3c mutant mice show long-term, incomplete retention of some afferent inner ear innervation.

Xiang M, Maklad A, Pirvola U, Fritzsch B - BMC Neurosci (2003)

BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c  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  mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC149366&req=5

Figure 9: BDNF and NT-3 mRNA expression is shown in the cochlea of P0 (a-d) and P8 (e,f) Brn3c 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 mice in an area that topologically compares to the inner hair cells of control animals (e,f, arrows). Bar indicates 100 μm.
Mentions: In the cochlea, the BDNF signal was very weak in the base in both the control (Fig. 9b) and the Brn3c littermates (Fig. 9a). However, there was a surprisingly strong NT-3 signal over the organ of Corti in the apex of Brn3c 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 mice (Fig. 9e,9f).

Bottom Line: At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin mutations.At postnatal day 7/8 (P7/8), innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base.Despite more severe loss of hair cells (1% compared to 20%), the cochlea retains many more sensory neurons (46% compared to 15%) than vestibular epithelia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Advanced Biotechnology and Medicine, Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. xiang@cabm.rutgers.edu

ABSTRACT

Background: Ears of Brn3c mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates. This partial development of hair cells could lead to enough neurotrophin expression to sustain sensory neurons through embryonic development. We have therefore investigated in these mutants the patterns of innervation and of expression of known neurotrophins.

Results: At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin mutations. At postnatal day 7/8 (P7/8), innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base. Around 20% of immature hair cells exist in the mutant vestibular sensory epithelia. Despite more severe loss of hair cells (1% compared to 20%), the cochlea retains many more sensory neurons (46% compared to 15%) than vestibular epithelia. Even 6 months old mutant mice have some fibers to all vestibular sensory epithelia and many more to the cochlear apex which lacks MyoVIIa positive hair cells. Topologically organized central cochlea projections exist at least until P8, suggesting that functional hair cells are not required to establish such projections.

Conclusion: The limited expression of neurotrophins in the cochlea of Brn3c mice suffices to support many sensory neurons, particularly in the cochlea, until birth. The molecular nature of the long term survival of apical spiral neurons remains unclear.

Show MeSH
Related in: MedlinePlus