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Overexpression of the transcription factor (TF) ATOH1 is known to induce the transformation of nonsensory cells in the organ of Corti into hair cells (HCs). Evaluating DNA 5′ to the coding sequence of the pou4f3 gene, a target of ATOH1 in HCs, we identified in three regions containing clustered binding sites for ATOH1 and several other TFs that are(More)
Neurotrophins participate in regulating the survival, differentiation, and target innervation of many neurons, mediated by high-affinity Trk and low-affinity p75 receptors. In the cochlea, spiral ganglion (SG) neuron survival is strongly dependent upon neurotrophic input, including brain-derived neurotrophic factor (BDNF), which increases the number of(More)
Extracellular matrix (ECM) molecules have been shown to function as cues for neurite guidance in various populations of neurons. Here we show that laminin (LN) and fibronectin (FN) presented in stripe micro-patterns can provide guidance cues to neonatal (P5) inner ear spiral ganglion (SG) neurites. The response to both ECM molecules was dose-dependent. In a(More)
Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret(More)
BACKGROUND Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, are commonly used as cholesterol-lowering drugs. During the past decade, evidence has emerged that statins also have neuroprotective effects. Research in the retina has shown that simvastatin, a commonly used statin, increases Akt phosphorylation in vivo, indicating(More)
L1, a neural cell adhesion molecule of the immunoglobulin superfamily, is widely expressed in the nervous system and important in axonal outgrowth, guidance, synapse formation, and signaling. Gene deletion studies emphasize the significance of L1 during development of the central nervous system and L1 is crucial for the topographic targeting of retinal(More)
Developmental changes in responsiveness of rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were examined using an explant culture system. Spiral ganglion (SG) explants at embryonic Day 18 (E18), postnatal Day 0 (P0), P5, P10 and P20 were cultured with the addition of either NT-3 or BDNF at various(More)
Neuron-glial-related cell adhesion molecule (NrCAM) is a neuronal cell adhesion molecule involved in neuron–neuron and neuron–glial adhesion as well as directional signaling during axonal cone growth. NrCAM has been shown to be involved in several cellular processes in the central and peripheral nervous systems, including neurite outgrowth, axonal(More)
OBJECTIVE Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the(More)
Matrix metalloproteinases (MMPs) play an important role in modeling of the extracellular matrix. There is increasing evidence that these proteases are important in neurite elongation and axonal guidance during development in the central nervous system and retina. Moreover, they are also expressed after acute injury and can be the key mediators of(More)