Math5 expression and function in the central auditory system
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 cen...
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Published in | Molecular and cellular neuroscience Vol. 37; no. 1; pp. 153 - 169 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.01.2008
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Current address: Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN (SMS); Department of Biological Structure, University of Washington, Seattle, WA (JAB) |
ISSN: | 1044-7431 1095-9327 |
DOI: | 10.1016/j.mcn.2007.09.006 |