Showing papers by "Michael Sendtner published in 1993"
TL;DR: It is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.
Abstract: CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a subpopulation of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.
577 citations
TL;DR: The results strongly suggest that oligodendrocyte survival depends upon the presence of axons and support the hypothesis that a competition for axon-dependent survival signals normally helps adjust the number of oligodendedrocytes to the numberof axons that require myelination.
276 citations
TL;DR: It is demonstrated that lesioned newborn rat facial motoneurons can be rescued by NT‐4/5, IGF‐I and LIF, which suggests that motoneuron survival and function are regulated by the coordinated actions of members of different gene families.
Abstract: The survival and functional maintenance of spinal motoneurons, both during the period of developmental cell death and in adulthood, have been shown to be dependent on trophic factors. In vitro experiments have previously been used to identify several survival factors for motoneurons, including CNTF, LIF, and members of the neurotrophin, FGF, and IGF gene families. Some of these factors have also been shown to be active in vivo, either on chick motoneurons during embryonic development or on lesioned facial and spinal motoneurons of the newborn rat. Here we demonstrate that lesioned newborn rat facial motoneurons can be rescued by NT-4/5, IGF-I and LIF. Furthermore, in contrast to chick motoneurons, the survival of isolated embryonic rat motoneurons can be maintained by the neurotrophins BDNF, NT-3, and NT-4/5. IGF-I and FGF-5 were also active in this system, each supporting more than 50% of the originally plated neurons. The responsiveness of motoneurons to multiple factors in vitro and in vivo suggests that motoneuron survival and function are regulated by the coordinated actions of members of different gene families. © 1993 Wiley-Liss, Inc.
267 citations
TL;DR: Results suggest that FGF-5 may act as a target-derived trophic factor for motoneurons, based on the fact that significant proportions of the motoneuron survival activity of rat skeletal muscle extracts could be immunoprecipitated using an antiserum to FGF -5.
138 citations
TL;DR: The goal of present and future investigations is to elucidate their (relative) physiological role during different stages of development, their possible pathophysiologi-cal importance, and, as a consequence, their suitability for the treatment of degenerative diseases of motoneu-rons such as amyotrophic lateral sclerosis.
83 citations
TL;DR: In astrocyte‐enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN‐γ and down‐regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family.
Abstract: The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyte enriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-"{. CNTF mRNA levels were down-regulated in these cells by treat ments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed. © 1993 Wiley-Liss, Inc.
43 citations
Journal Article•
TL;DR: Secretory molecules which are expressed in skeletal muscle during embryonic development and which support motoneurons in culture and partially also in vivo include members of the NGF gene family (BDNF, NT-3,NT-4/5), FGF-5, IGF-I, and LIF.
Abstract: Motoneurons played an essential role in establishing the concept of target-mediated support of innervating neurons. However, it took several decades until molecules were identified which trophically support motoneurons in vitro and in vivo. The most potent molecule identified so far is ciliary neurotrophic factor (CNTF). It is expressed as a cytosolic molecule in myelinating Schwann cells rather than in skeletal muscle in the postnatal period and therefore does not qualify as a target-derived neurotrophic factor regulating motoneuron survival during embryonic development. However, the inactivation of CNTF by gene targeting experiments results in progressive atrophy and degeneration of motoneurons, demonstrating that CNTF plays an essential role as a maintenance factor for motoneurons postnatally. Secretory molecules which are expressed in skeletal muscle during embryonic development and which support motoneurons in culture and partially also in vivo include members of the NGF gene family (BDNF, NT-3, NT-4/5), FGF-5, IGF-I, and LIF. The evaluation of the physiological importance of these molecules is under investigation.
13 citations
TL;DR: The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation of CNTF mRNA levels in cultured glial cells were investigated and three-week-old astrocyte-enriched cell cultures from new-born rat brain contained easily detectableCNTF mRNA.
Abstract: The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation of CNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyte-enriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed
4 citations