Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation in vivo and in vitro.
The olfactory epithelium (OE) of the mouse provides a unique system for understanding how cell birth and cell death interact to regulate neuron number during development and regeneration. We have examined cell death in the OE in normal adult mice; in adult mice subjected to unilateral olfactory bulbectomy (surgical removal of one olfactory bulb, the synaptic target of olfactory receptor neurons (ORNs) of the OE); and in primary cell cultures derived from embryonic mouse OE. In vivo, cells at all stages in the neuronal lineage--proliferating neuronal precursors, immature ORNs, and mature ORNs--displayed signs of apoptotic cell death; nonneuronal cells did not. Bulbectomy dramatically increased the number of apoptotic cells in the OE on the bulbectomized side. Shortly following bulbectomy, increased cell death involved neuronal cells of all stages. Later, cell death remained persistently elevated, but this was due to increased apoptosis by mature ORNs alone. In vitro, apoptotic death of both ORNs and their precursors could be inhibited by agents that prevent apoptosis in other cells: aurintricarboxylic acid (ATA), a membrane-permeant anlog of cyclic AMP (CPT-cAMP), and certain members of the neurotrophin family of growth factors (brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 5), although no neurotrophin was as effective at promoting survival as ATA or CPT-cAMP. Consistent with observed effects of neurotrophins, immunohistochemistry localized the neurotrophin receptors trkB and trkC to fractions of ORNs scattered throughout neonatal OE. These results suggest that apoptosis may regulate neuronal number in the OE at multiple stages in the neuronal lineage and that multiple factors-potentially including certain neurotrophins--may be involved in this process.
Holcomb
J D
JD
Department of Biological Sciences, University of Iowa, Iowa City 52242, USA.
Mumm
J S
JS
Calof
A L
AL
D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004848:Epithelium / Q000196:embryology / Q000294:innervation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3; D009830:Olfactory Bulb / Q000502:physiology*; D009831:Olfactory Mucosa / Q000196:embryology / Q000294:innervation*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011994:Recombinant Proteins; C071951:neurotrophin 5; D004247:DNA