Neurotrophins are small proteins vital for neuronal growth, differentiation, survival, and plasticity [1]. Members of the mammalian neurotrophin family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotro‐ phin-4/5 (NT-4/5). Their neurotrophic effects are mediated by the tropomyosin receptor kin‐ ase (Trk) receptors, membrane-bound rec...

Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the mac...

The intracellular domain of the p75 neurotrophin receptor (p75ICD) can be released by gamma-secretase in response to the previous activation of alpha-secretase by phorbol esters. However, ligand-dependent release of p75ICD has yet to be described. We show here that nerve growth factor can induce the release of p75ICD and facilitate its translocation to the nucleus in a gamma-secretase-dependent...

In the nervous system, communication between neurons and their post-synaptic target cells is critical for the formation, refinement and maintenance of functional neuronal connections. Diffusible signals secreted by target tissues, exemplified by the family of neurotrophins, impinge on nerve terminals to influence diverse developmental events including neuronal survival and axonal growth. Key me...

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotroph...

A role for neurotrophins in mature primary sensory neurons persists, extending beyond that of promoting survival during development, to one of maintaining phenotypic and functional properties. Many adaptive changes that occur after peripheral axotomy and in axonal repair are believed to be influenced by altered availability of neurotrophic molecules to the neuron in this state. Indeed, administ...

Neurotrophin-mediated cell survival and differentiation of vertebrate neurons is caused by ligand-specific binding to the Trk family of tyrosine kinase receptors. However, sites in the neurotrophins responsible for the binding to Trk receptors and the mechanisms whereby this interaction results in receptor activation and biological activity are unknown. Here we show that in nerve growth factor ...

Neonatal sciatic nerve injury is known to result in an extensive loss of lumbar motor neurons as well as the disappearance of their respective muscle fibers in the hindlimb musculature. The loss of motor neurons and muscle fibers can be prevented by immediate administration of target-derived neurotrophic factors to the site of injury. In the present study, we investigated the role of ciliary ne...

Axonal target-derived BMP and neurotrophin signaling are both known to regulate neuronal gene expression, differentiation, and axon growth. In this issue of Neuron, Ji and Jaffrey (2012) discovered that BMP-signaling endosomes depend on BDNF-induced axonal synthesis of SMADs to retrogradely regulate transcription in developing trigeminal neurons, providing a mechanism of integrating the two tar...

Null mutations affecting members of the transforming growth factor-beta and neurotrophin families result in overlapping patterns of neuronal cell death. This is particularly striking in the cranial sensory nodose-petrosal ganglion complex (NPG), in which loss of either glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotr...