Affiliation:
1. Laboratory of Developmental Neurobiology, National Institutes of Health, National Institute of Child Health and Human Development, Building 49, Room 5A38, 49 Convent Drive, Bethesda, MD 20892, USA.
Abstract
Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes. We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca
2+
, Ca
2+
/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3′,5′-monophosphate response element binding protein, and expression of c-
fos
and
Krox-24
. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.
Publisher
American Association for the Advancement of Science (AAAS)
Reference49 articles.
1. Developmental mechanisms that generate precise patterns of neuronal connectivity
2. Confocal microscopy (MRC 1024 Bio-Rad Hercules GA) with the Ca 2+ -sensitive indicator fluo-3/AM (Molecular Probes Eugene OR) was used to measure changes in fluorescence intensity (Δ F / F o ) due to Ca 2+ transients in SCs and DRG neurons in a Hepes-buffered balanced salt solution (pH 7.2) at room temperature (33). Nikon ×40 0.7 numerical aperture (NA) long working distance and 1.3 NA objectives were used for plastic culture dishes and cover slips respectively. Confocal microscopy excludes fluorescent signals from cells outside the plane of focus and enables unambiguous distinction of Ca 2+ responses in SCs from responses in neurons and axons. Ca 2+ transients in response to bath application of ATP (Molecular Probes) were also measured in SCs grown in monoculture for 24 to 72 hours.
3. Axonal activation-induced calcium transients in myelinating Schwann cells, sources, and mechanisms
4. Neurally evoked calcium transients in terminal Schwann cells at the neuromuscular junction.
5. Transmitter release increases intracellular calcium in perisynaptic schwann cells in situ
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