Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons.
Leukemia inhibitory factor (LIF; also known as cholinergic differentiation factor) is a multifunctional cytokine that affects neurons, as well as many other cell types. To examine its neuronal functions in vivo, we have used LIF-deficient mice. In culture, LIF alters the transmitter phenotype of sympathetic neurons, inducing cholinergic function, reducing noradrenergic function, and altering neuropeptide expression. In vivo, a noradrenergic to cholinergic switch occurs in the developing sweat gland innervation, and changes in neuropeptide phenotype occur in axotomized adult ganglia. We find that the gland innervation of LIF-deficient mice is indistinguishable from normal. In contrast, neuropeptide induction in ganglia cultured as explants or axotomized in situ is significantly suppressed in LIF-deficient mice. Thus, LIF plays a role in transmitter changes induced by axotomy but not by developmental interactions with sweat glands.
Rao
M S
MS
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106.
Sun
Y
Y
Escary
J L
JL
Perreau
J
J
Tresser
S
S
Patterson
P H
PH
Zigmond
R E
RE
Brulet
P
P
Landis
S C
SC
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003433:Crosses, Genetic; D017931:DNA Primers; D005260:Female; D019004:Galanin; D005728:Ganglia, Sympathetic / Q000502:physiology*; D017353:Gene Deletion; D006131:Growth Inhibitors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
D017931:DNA Primers; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009479:Neuropeptides; D010455:Peptides; D014660:Vasoactive Intestinal Peptide; D015288:Neurokinin A; D019004:Galanin