RT Journal Article
SR Electronic
T1 Loss of Leukemia Inhibitory Factor Receptor β or Cardiotrophin-1 Causes Similar Deficits in Preganglionic Sympathetic Neurons and Adrenal Medulla
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1823
OP 1832
DO 10.1523/JNEUROSCI.4127-05.2006
VO 26
IS 6
A1 Stephan Oberle
A1 Andreas Schober
A1 Verena Meyer
A1 Bettina Holtmann
A1 Christopher Henderson
A1 Michael Sendtner
A1 Klaus Unsicker
YR 2006
UL http://www.jneurosci.org/content/26/6/1823.abstract
AB Leukemia inhibitory factor (LIF) receptor β (LIFRβ) is a receptor for a variety of neurotrophic cytokines, including LIF, ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1). These cytokines play an essential role for the survival and maintenance of developing and postnatal somatic motoneurons. CNTF may also serve the maintenance of autonomic, preganglionic sympathetic neurons (PSNs) in the spinal cord, as suggested by its capacity to prevent their death after destruction of one of their major targets, the adrenal medulla. Although somatic motoneurons and PSNs share a common embryonic origin, they are distinct in several respects, including responses to lesions. We have studied PSNs in mice with targeted deletions of the LIFRβ or CT-1 genes, respectively. We show that LIF, CNTF, and CT-1 are synthesized in embryonic adrenal gland and spinal cord and that PSNs express LIFRβ. In embryonic day 18.5 LIFRβ (−/−) and CT-1 (−/−) mice, PSNs were reduced by ∼20%. PSNs projecting to the adrenal medulla were more severely affected (−55%). Although LIFRβ (−/−) mice revealed normal numbers of adrenal chromaffin cells and axons terminating on chromaffin cells, levels of adrenaline and numbers of adrenaline-synthesizing cells were significantly reduced. We conclude that activation of LIFRβ is required for normal development of PSNs and one of their prominent targets, the adrenal medulla. Thus, both somatic motoneurons and PSNs in the spinal cord depend on LIFRβ signaling for their development and maintenance, although PSNs seem to be overall less affected than somatic motoneurons by LIFRβ deprivation.