Changes in Sef levels influence auditory brainstem development and function
| Autor: | C. Lu, Andrew F. Tucker, Donald E. Coling, N. Hyun, Victoria E. Abraira, G. R. Hoffman, Lisa V. Goodrich, M. C. Brown |
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| Rok vydání: | 2007 |
| Předmět: |
Nervous system
Cochlear Nucleus General Neuroscience Fibroblast growth factor receptor 1 Membrane Proteins Chick Embryo Articles Biology Immunohistochemistry Cochlear nucleus Fibroblast Growth Factors Mice Mice Neurologic Mutants Auditory brainstem response medicine.anatomical_structure Auditory nuclei medicine Evoked Potentials Auditory Brain Stem Morphogenesis Auditory system Animals Brainstem Neuroscience Rhombic lip Brain Stem |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(16) |
| ISSN: | 1529-2401 |
| Popis: | During development of the CNS, secreted morphogens of the fibroblast growth factor (FGF) family have multiple effects on cell division, migration, and survival depending on where, when, and how much FGF signal is received. The consequences of misregulating the FGF pathway were studied in a mouse with decreased levels of the FGF antagonistSef. To uncover effects in the nervous system, we focused on the auditory system, which is accessible to physiological analysis. We found that the mitogen-activated protein kinase pathway is active in the rhombic lip, a germinal zone that generates diverse types of neurons, including the cochlear nucleus complex of the auditory system.Sefis expressed immediately adjacent to the rhombic lip, overlapping withFGF15andFGFR1, which is also present in the lip itself. This pattern suggests that Sef may normally function in non-rhombic lip cells and prevent them from responding to FGF ligand in the vicinity. Consistent with this idea, overexpression ofSefin chicks decreased the size of the auditory nuclei. Cochlear nucleus defects were also apparent in mice with reduced levels ofSef, with 13% exhibiting grossly dysmorphic cochlear nuclei and 26% showing decreased amounts of GFAP in the cochlear nucleus. Additional evidence for cochlear nucleus defects was obtained by electrophysiological analysis ofSefmutant mice, which have normal auditory thresholds but abnormal auditory brainstem responses. These results show both increases and decreases in Sef levels affect the assembly and function of the auditory brainstem. |
| Databáze: | OpenAIRE |
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