In vivo role for CREB signaling in the noradrenergic differentiation of sympathetic neurons.
Signaling pathways involving cAMP and CREB have been implicated in several aspects of sympathetic neuron differentiation. Here, we used in vivo loss-of-function approaches in both mouse and chick embryos to characterize the physiological role of cAMP/CREB. Whereas sympathetic neuron development proceeds normally in CREB-deficient mouse embryos, a decrease in noradrenergic differentiation (TH, DBH) was observed in chick sympathetic ganglia in response to ACREB, a dominant-negative CREB variant which interferes with the function of all CREB family members. In contrast, expression of the generic neuronal marker SCG10 was not affected by ACREB. As the decrease in noradrenergic gene expression is compensated at later stages of development and TH expression in differentiated neurons is not CREB-dependent, a transient role for CREB is proposed, accelerating noradrenergic but not generic neuronal differentiation of sympathetic neurons.
Rüdiger
Roland
R
RG Developmental Neurobiology, Department Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstr. 46, D-60528 Frankfurt/M, Germany.
Binder
Ellen
E
Tsarovina
Konstantina
K
Schmidt
Mirko
M
Reiff
Tobias
T
Stubbusch
Jutta
J
Rohrer
Hermann
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D018398:Homeodomain Proteins; C491060:Phox2a protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine