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Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate both short-term synaptic functions and long-term potentiation (LTP) of brain synapses, raising the possibility that BDNF/TrkB may be involved in cognitive functions. We have generated conditionally gene targeted mice in which the knockout of the trkB gene is restricted to the forebrain(More)
The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal lobes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with(More)
Chemical synapses contain specialized pre- and postsynaptic structures that regulate synaptic transmission and plasticity. EphB receptor tyrosine kinases are important molecular components in this process. Previously, EphB receptors were shown to act postsynaptically, whereas their transmembrane ligands, the ephrinBs, were presumed to act presynaptically.(More)
The TrkB receptor tyrosine kinase and its ligand, BDNF, have an essential role in certain forms of synaptic plasticity. However, the downstream pathways required to mediate these functions are unknown. We have studied mice with a targeted mutation in either the Shc or the phospholipase Cgamma (PLCgamma) docking sites of TrkB (trkB(SHC/SHC) and trkB(PLC/PLC)(More)
Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons in culture. In vivo, NGF decreases the extent of naturally occurring cell death in developing sympathetic ganglia and protects cholinergic neurons of the basal forebrain and caudatoputamen. NGF interacts with the low-affinity p75 receptor(More)
The trkC gene is expressed throughout the mammalian nervous system and encodes a series of tyrosine protein kinase isoforms that serve as receptors for neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of neurotrophic factors. One of these isoforms, gp145trkC/TrkC K1, mediates the trophic properties of NT3 in cultured cells. Here we(More)
We have exploited a battery of approaches to address several controversies that have accompanied the expansion of the nerve growth factor (NGF) family of neurotrophic factors and the identification of the Trk tyrosine kinases as receptors for these factors. For example, we find that a recently cloned mammalian neurotrophin, known as either neurotrophin-4 or(More)
Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections(More)
We have generated mice carrying a germline mutation in the tyrosine kinase catalytic domain of the trkB gene. This mutation eliminates expression of gp145trkB, a protein-tyrosine kinase that serves as the signaling receptor for two members of the nerve growth factor family of neurotrophins, brain-derived neurotrophic factor and neurotrophin-4. Mice(More)
We previously identified two tyrosine protein kinase genes, designated trk and trkB, that code for putative neurogenic cell surface receptors. In this study, we report that the mouse trkB locus codes for at least two classes of receptor-like molecules. These trkB proteins, designated gp145trkB and gp95trkB, have identical extracellular and transmembrane(More)