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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)
Transcription factors (TFs) can regulate different sets of genes to determine specific cell types by means of combinatorial codes. We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival. These motifs, 100% conserved among four(More)
Apoptotic cell death is considered to play a key role in gentamicin-induced cochlear hair cell loss. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis that can prevent activation of effector caspases. This study was designed to investigate the possible involvement of X-linked inhibitor of apoptosis protein (XIAP) in hair cell(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)
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)
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)
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)
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)
Adenovirus vectors (AdVs) are efficient tools for gene therapy in many tissues. Several studies have demonstrated successful transgene transduction with AdVs in the inner ear of rodents [Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y (2003) J Neurosci 23:4395-4400]. However, toxicity of AdVs [Morral N, O'Neal WK, Rice K, Leland MM, Piedra PA,(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)