Developmental Requirement of gp130 Signaling in Neuronal Survival and Astrocyte Differentiation

Abstract

gp130 is a signal-transducing receptor component used in common by the interleukin-6 (IL-6) family of hematopoietic and neurotrophic cytokines, including IL-6, IL-11, leukemia-inhibitory factor, ciliary neurotrophic factor, oncostatin-M, and cardiotrophin-1. We have examined in this study a role of gp130 in the nervous system by analyzing developmental cell death of several neuronal populations and the differentiation of astrocytes in gp130-deficient mice. A significant reduction was observed in the number of sensory neurons in L5 dorsal root ganglia and motoneurons in the facial nucleus, the nucleus ambiguus, and the lumbar spinal cord in gp130 -/- mice on embryonic day 18.5. On the other hand, no significant neuronal loss was detectable on day 14.5, suggesting a physiological role of gp130 in supporting newly generated neurons during the late phase of development when naturally occurring cell death takes place. Moreover, expression of an astrocyte marker, GFAP, was severely reduced in the brain of gp130 -/- mice. Our data demonstrate that gp130 expression is essential for survival of subgroups of differentiated motor and sensory neurons and for the differentiation of major populations of astrocytes in vivo.