Math5 expression and function in the central auditory system

Sara M. Saul, Joseph A. Brzezinski IV, Richard A. Altschuler, Susan E. Shore, Dellaney D. Rudolph, Lisa L. Kabara, Karin E. Halsey, Robert B. Hufnagel, Jianxun Zhou, David F. Dolan, Thomas M Glaser

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The basic helix-loop-helix (bHLH) transcription factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5-lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 -/- mice compared to Math5 +/- mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 -/- mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II-IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

Original languageEnglish (US)
Pages (from-to)153-169
Number of pages17
JournalMolecular and Cellular Neuroscience
Volume37
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Fingerprint

Cochlear Nucleus
Neurons
Rhombencephalon
Brain Stem Auditory Evoked Potentials
Auditory Perceptual Disorders
Basic Helix-Loop-Helix Transcription Factors
Cochlear Nerve
Retinal Ganglion Cells
Potassium Channels
Cochlea
Neurogenesis
Optic Nerve
Lip
Transgenes
Knockout Mice
Brain Stem
Embryonic Development
In Situ Hybridization
Alkaline Phosphatase
Messenger RNA

Keywords

  • ABR latency
  • atonal
  • Auditory processing
  • AVCN
  • bHLH
  • Binaural integration
  • Calyx of Held
  • Cochlear nucleus
  • Cochlear root neurons
  • Cre recombinase
  • Fluoro-Gold
  • Globular bushy cells
  • Inferior colliculus
  • Interaural intensity difference
  • Interaural time difference
  • Kcnq4
  • Kv1.1
  • Kv3.1
  • MafB
  • Math1
  • Math5
  • Mouse
  • Multipolar cells
  • Phase locking
  • PVCN
  • Rhombic lip
  • Spherical bushy cells
  • Tract-tracing

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Saul, S. M., Brzezinski IV, J. A., Altschuler, R. A., Shore, S. E., Rudolph, D. D., Kabara, L. L., ... Glaser, T. M. (2008). Math5 expression and function in the central auditory system. Molecular and Cellular Neuroscience, 37(1), 153-169. https://doi.org/10.1016/j.mcn.2007.09.006

Math5 expression and function in the central auditory system. / Saul, Sara M.; Brzezinski IV, Joseph A.; Altschuler, Richard A.; Shore, Susan E.; Rudolph, Dellaney D.; Kabara, Lisa L.; Halsey, Karin E.; Hufnagel, Robert B.; Zhou, Jianxun; Dolan, David F.; Glaser, Thomas M.

In: Molecular and Cellular Neuroscience, Vol. 37, No. 1, 01.2008, p. 153-169.

Research output: Contribution to journalArticle

Saul, SM, Brzezinski IV, JA, Altschuler, RA, Shore, SE, Rudolph, DD, Kabara, LL, Halsey, KE, Hufnagel, RB, Zhou, J, Dolan, DF & Glaser, TM 2008, 'Math5 expression and function in the central auditory system', Molecular and Cellular Neuroscience, vol. 37, no. 1, pp. 153-169. https://doi.org/10.1016/j.mcn.2007.09.006
Saul SM, Brzezinski IV JA, Altschuler RA, Shore SE, Rudolph DD, Kabara LL et al. Math5 expression and function in the central auditory system. Molecular and Cellular Neuroscience. 2008 Jan;37(1):153-169. https://doi.org/10.1016/j.mcn.2007.09.006
Saul, Sara M. ; Brzezinski IV, Joseph A. ; Altschuler, Richard A. ; Shore, Susan E. ; Rudolph, Dellaney D. ; Kabara, Lisa L. ; Halsey, Karin E. ; Hufnagel, Robert B. ; Zhou, Jianxun ; Dolan, David F. ; Glaser, Thomas M. / Math5 expression and function in the central auditory system. In: Molecular and Cellular Neuroscience. 2008 ; Vol. 37, No. 1. pp. 153-169.
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AU - Brzezinski IV, Joseph A.

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AU - Shore, Susan E.

AU - Rudolph, Dellaney D.

AU - Kabara, Lisa L.

AU - Halsey, Karin E.

AU - Hufnagel, Robert B.

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N2 - The basic helix-loop-helix (bHLH) transcription factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5-lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 -/- mice compared to Math5 +/- mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 -/- mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II-IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

AB - The basic helix-loop-helix (bHLH) transcription factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5-lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 -/- mice compared to Math5 +/- mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 -/- mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II-IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

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KW - atonal

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KW - AVCN

KW - bHLH

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KW - Calyx of Held

KW - Cochlear nucleus

KW - Cochlear root neurons

KW - Cre recombinase

KW - Fluoro-Gold

KW - Globular bushy cells

KW - Inferior colliculus

KW - Interaural intensity difference

KW - Interaural time difference

KW - Kcnq4

KW - Kv1.1

KW - Kv3.1

KW - MafB

KW - Math1

KW - Math5

KW - Mouse

KW - Multipolar cells

KW - Phase locking

KW - PVCN

KW - Rhombic lip

KW - Spherical bushy cells

KW - Tract-tracing

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