Adult rat otic placode-derived neurons and sensory epithelium express all four erbB receptors: a role in regulating vestibular ganglion neuron viability.
The erbB receptor family consists of erbB1/epidermal growth factor receptor, erbB2/neu, erbB3, and erbB4, all of which have been implicated in cell proliferation, differentiation, and survival in several tissues. In the nervous system, these family members can function in a trophic capacity for certain subpopulations of neurons and some types of non-neuronal cells. Vestibular sensory epithelial cells and vestibular ganglion neurons are derived from ectodermal otic placode and are essential components of the peripheral vestibular system, the sensory system for balance. Recent studies in mammals suggest that certain ligands of the epidermal growth factor receptor can induce proliferation of vestibular sensory epithelial cells. We now show that vestibular ganglion neurons and vestibular sensory epithelial cells express all four erbB receptors in adult rats. Cultured vestibular ganglion neurons also expressed all four erbB family members and were therefore used to analyze the effects of modulating erbB signaling on differentiated vestibular ganglion neurons. Transforming growth factor-alpha (a ligand for epidermal growth factor receptor) and sensory and motor neuron-derived factor (a ligand for erbB3 and erbB4) promoted vestibular ganglion neuron viability, whereas epidermal growth factor (another ligand for epidermal growth factor receptor) did not. Glial growth factor 2 (another ligand for erbB3 and erbB4) and an antibody that blocks erbB2/neu-mediated signaling inhibited vestibular ganglion neuron viability. Collectively, these observations indicate that erbB signaling regulates the viability of differentiated otic placode-derived cells in mammals and suggest that exogenous modulation of erbB signaling in peripheral vestibular tissues may prove therapeutically useful in peripheral vestibular disorders.
Matsunaga
T
T
Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Davis
J G
JG
Greene
M I
MI
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005455:Fluorescent Antibody Technique; D017950:Ganglia, Sensory / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012444:Saccule and Utricle / Q000378:metabolism; D015398:Signal Transduction; D014722:Vestibule, Labyrinth / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587691:Erbb4 protein, rat