Results: 5

1.
Fig. 1.

Fig. 1. From: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.

Loss of erbB signaling in SCs causes vestibular dysfunction. (A) VsEPs from WT and GFAP-DN-erbB4 Tg mice demonstrate the severity of vestibular dysfunction at P21. Magnitude of the evoking head jerk is expressed in dB re: 1.0 g/ms. (B) Box plot analysis of VsEP thresholds: arrow illustrates the threshold shift in GFAP-DN-erbB4 mice, which had no response at the highest levels tested (ND, not detectable). (C) Box plot analysis of peak 1 amplitudes for VsEPs at 5 dB for WT (n = 4) and GFAP-DN-erbB4 mice (n = 4); ***P < 0.0001.

Maria E. Gómez-Casati, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17005-17010.
2.
Fig. 3.

Fig. 3. From: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.

BDNF expression is reduced in GFAP-DN-erbB4 utricles. (A) Real-time quantitative RT-PCR shows BDNF mRNA is reduced at P26 in GFAP-DN-erbB4 (n = 6) compared with WT (n = 9) mice; ***P = 0.0002. In contrast, expression of two other trophic factors, GDNF and NT3, is unaffected (P = 0.63 and P = 0.34 for GDNF and NT3, respectively). (B) Immunostaining of utricular maculae shows reduced BDNF expression in GFAP-DN-erbB4 mice at P10 (Inset: high-magnification image). [Scale bars: 50 μm, 10 μm (Inset).] (C) Quantification of BDNF fluorescence (arbitrary units) in utricular maculae of P10 WT (n = 6) and GFAP-DN-erbB4 (n = 4) mice; *P = 0.0155. Error bars represent SEMs.

Maria E. Gómez-Casati, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17005-17010.
3.
Fig. 2.

Fig. 2. From: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.

Loss of erbB signaling in SCs causes defects in synapse formation. (A) Immunostaining for synapses [seen as colocalization of the pre- and postsynaptic markers RIBEYE (red) and GluR2/3 (green)] reveals a reduction in afferent synapses on utricular hair cells in P21 GFAP-DN-erbB4 mice (hair cell region delineated by fine white line). [Scale bars: 50 μm, 10 μm (Inset).] (B) Mean synaptic density (colocalized RIBEYE and GluR2/3), presynaptic ribbons (RIBEYE puncta), and postsynaptic receptor plaques (GluR2/3 puncta) from three to six utricles at each postnatal age. Error bars represent SEMs.

Maria E. Gómez-Casati, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17005-17010.
4.
Fig. 4.

Fig. 4. From: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.

Knockdown of BDNF expression in SCs results in vestibular dysfunction and loss of synapses. Box plot analysis of VsEP thresholds (A) and peak 1 amplitudes at 5 dB (B) from control (BDNFf/f; n = 12) and BDNF conditional KO (BDNFf/f::PLP/CreERT; n = 9) mice injected with tamoxifen from embryonic day (E) 14.5 to E17.5 show that BDNF knockdown leads to vestibular dysfunction at P26. Magnitude of the evoking head jerk is expressed in dB re: 1.0 g/ms; ***P < 0.0001. (C) BDNF immunostaining of P26 utricular maculae from tamoxifen treated control and conditional KO mice illustrates the successful knockout of BDNF. (Scale bar, 20 μm.) (D) Quantification of synapses (colocalized RIBEYE and GluR2/3), presynaptic ribbons (RIBEYE puncta), and postsynaptic receptor plaques (GluR2/3 puncta) from BDNFf/f (n = 7), BDNFf/f::PLP/CreERT (n = 6), and GFAP-DN-erbB4 (n = 4) utricles show that reduced BDNF expression in SCs reduces synaptic density; ***P < 0.0001. Error bars in D represent SEM.

Maria E. Gómez-Casati, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17005-17010.
5.
Fig. 5.

Fig. 5. From: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.

BDNF reexpression in SCs rescues vestibular function and synapse formation in GFAP-DN-erbB4 mice. (A) BDNF immunostaining of P26 utricular, maculae from control (BDNFstop), GFAP-DN-erbB4 mice carrying the BDNFstop transgene, and mice carrying all three transgenes (GFAP-DN-erbB4, BDNFstop and PLP/CreERT) show that tamoxifen increases BDNF expression in SCs of the utricular macula of BDNFstop::GFAP-DN-erbB4::PLP/CreERT mice to levels similar to those of control mice. (Scale bar, 20 μm.) Box plot analysis of VsEP thresholds: arrow illustrates the threshold shift in GFAP-DN-erbB4 mice, which had no response at the highest levels tested (ND, not detectable) (B) and peak 1 amplitudes at 5 dB (C) from control mice (n = 6), GFAP-DN-erbB4 mice carrying the BDNFstop transgene (n = 6), and mice carrying all three transgenes (n = 4) show that conditional overexpression of BDNF rescues the vestibular function of GFAP-DN-erbB4 mice at P26. Magnitude of the evoking head jerk is expressed in dB re: 1.0 g/ms; ***P < 0.0001. (D) Quantification of synapses (colocalized RIBEYE and GluR2/3), presynaptic ribbons (RIBEYE puncta), and postsynaptic receptor plaques (GluR2/3 puncta) in utricular maculae of the same mice tested in AC shows that BDNF overexpression in SCs rescues the synaptic loss in GFAP-DN-erbB4 mice; ***P < 0.0001. Error bars in D represent SEMs.

Maria E. Gómez-Casati, et al. Proc Natl Acad Sci U S A. 2010 September 28;107(39):17005-17010.

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