The muscle-derived factors required for survival of embryonic motoneurons are not clearly identified. Cardiotrophin-1 (CT-1), a cytokine related to ciliary neurotrophic factor (CNTF), is expressed at high levels in embryonic limb bud and is secreted by differentiated myotubes. In vitro, CT-1 kept 43% of purified E14 rat motoneurons alive for 2 weeks (EC50 =… (More)
The cytokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) signal through a receptor complex formed between two transmembrane proteins, gp130 and LIFRbeta. In addition, CNTF also uses a ligand-binding component which is anchored to the cell membrane. In the case of cardiotrophin-1 (CT-1), LIFRbeta is also required in… (More)
Muscle-derived factors are known to be important for the survival of developing spinal motoneurons, but the molecules involved have not been characterized. Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in muscle development and motoneuron axon outgrowth. We show that HGF/SF has potent neurotrophic activity (EC50=2 pM) for a… (More)
The survival of central neurons depends on multiple neurotrophic factors produced by different cell types. We demonstrate that media conditioned by muscle and Schwann cell lines show strong synergistic effects on survival of purified embryonic day 14.5 rat motoneurons in culture. Different lines of evidence implicate glial cell line-derived neurotrophic… (More)
We have characterized different neuronal subpopulations derived from in vitro differentiation of embryonic stem (ES) cells using as markers the expression of several homeodomain transcription factors. Following treatment of embryo-like aggregates with retinoic acid (RA), Pax-6, a protein expressed by ventral central nervous system (CNS) progenitors is… (More)
The precise control of motor neuron (MN) death and survival following initial innervation of skeletal muscle targets is a key step in sculpting a functional motor system, but how this is regulated at the level of individual motor pools remains unclear. Hepatocyte growth factor (HGF) and its receptor Met play key developmental roles in both muscle and MNs.… (More)
More than 10 factors from different gene families are now known to enhance motoneuron survival, and to be expressed in a manner consistent with a role in regulating motoneuron numbers during development. We provide evidence that: a) different factors may act on different sub-populations of motoneurons; b) different factors may act in synergy on a given… (More)
legend: Bone marrow chimeric mice that received no irradiation (back), whole-body irradiation (middle), or head-protected irradiation (front). Cover art by Alexander Mildner. For more information, see the article by Mildner et al. in this issue (pages 11159 –11171).