Different factors from the central nervous system and periphery regulate the survival of sensory neurones

Work on nerve growth factor has established that the survival of developing vertebrate neurones depends on the supply of a neurotrophic factor from their target field1–5. The discovery of several new neurotrophic factors6 has raised the possibility that neurones which innervate multiple target fields require several different neurotrophic factors for survival. Here we show that two distinct neurotrophic factors, one in the central nervous system (CNS) and the other in skeletal muscle, promote the survival of proprioceptive neurones in culture. At saturating concentrations, either factor alone supported most neurones and there was no additional survival in the presence of both factors, but at sub-saturating concentrations the combined effect was additive. The neurotrophic activity of each factor was greatest during the period of natural neuronal death. Our results demonstrate that each cultured proprioceptive neurone responds to two distinct neurotrophic factors present in its respective central and peripheral target fields, and suggest that these factors cooperate in regulating survival during development.

[1]  H. Thoenen,et al.  The heparin‐binding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival. , 1984, The EMBO journal.

[2]  H. Thoenen,et al.  Placode and neural crest-derived sensory neurons are responsive at early developmental stages to brain-derived neurotrophic factor. , 1985, Developmental biology.

[3]  H. Thoenen,et al.  Nerve growth factor supply for sensory neurons: Site of origin and competition with the sympathetic nervous system , 1985, Neuroscience Letters.

[4]  L. Reichardt,et al.  Expression of the beta-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[5]  V. Hamburger,et al.  Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  H. Yip,et al.  Developing dorsal root ganglion neurons require trophic support from their central processes: evidence for a role of retrogradely transported nerve growth factor from the central nervous system to the periphery. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Fawcett,et al.  Regressive events in neurogenesis. , 1984, Science.

[8]  H. Thoenen,et al.  New neurotrophic factors. , 1983, Annual review of physiology.

[9]  H. Thoenen,et al.  Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues. , 1984, The EMBO journal.

[10]  E. Manni,et al.  JAW MUSCLE PROPRIOCEPTION AND MESENCEPHALIC TRIGEMINAL CELLS IN BIRDS. , 1965, Experimental neurology.

[11]  H. Thoenen,et al.  Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Davies,et al.  Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor , 1983, Nature.

[13]  W. Cowan,et al.  The development of the mesencephalic nucleus of the trigeminal nerve in the chick , 1973, The Journal of comparative neurology.

[14]  A. Davies,et al.  Relation of target encounter and neuronal death to nerve growth factor responsiveness in the developing mouse trigeminal ganglion , 1984, The Journal of comparative neurology.

[15]  H. Thoenen,et al.  Purification of a new neurotrophic factor from mammalian brain. , 1982, The EMBO journal.

[16]  H. Thoenen,et al.  Physiology of nerve growth factor. , 1980, Physiological reviews.

[17]  Eugene M. Johnson,et al.  Central nervous system and peripheral nerve growth factor provide trophic support critical to mature sensory neuronal survival , 1985, Nature.