Sexually dimorphic BDNF signaling directs sensory innervation of the mammary gland.

How neural circuits associated with sexually dimorphic organs are differentially assembled during development is unclear. Here, we report a sexually dimorphic pattern of mouse mammary gland sensory innervation and the mechanism of its formation. Brain-derived neurotrophic factor (BDNF), emanating from mammary mesenchyme and signaling through its receptor TrkB on sensory axons, is required for establishing mammary gland sensory innervation of both sexes at early developmental stages.

Deletion of the BDNF truncated receptor TrkB.T1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.

Brain Derived Neurotrophic Factor (BDNF) exerts strong pro-survival effects on developing and injured motoneurons. However, in clinical trials, BDNF has failed to benefit patients with amyotrophic lateral sclerosis (ALS). To date, the cause of this failure remains unclear.

Tamalin is a critical mediator of electroconvulsive shock-induced adult neuroplasticity.

The molecular mechanisms underlying the effects of electroconvulsive shock (ECS) therapy, a fast-acting and very effective antidepressant therapy, are poorly understood. Changes related to neuroplasticity, including enhanced adult hippocampal neurogenesis and neuronal arborization, are believed to play an important role in mediating the effects of ECS. Here we show a dynamic upregulation of the scaffold protein tamalin, selectively in the hippocampus of animals subjected to ECS.

Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo.

Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor.

In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues neuronal cell death in a trisomic mouse model.

Imbalances in neurotrophins or their high-affinity Trk receptors have long been reported in neurodegenerative diseases. However, a molecular link between these gene products and neuronal cell death has not been established. In the trisomy 16 (Ts16) mouse there is increased apoptosis in the cortex, and hippocampal neurons undergo accelerated cell death that cannot be rescued by administration of brain-derived neurotrophic factor (BDNF).

The scaffold protein Cybr is required for cytokine-modulated trafficking of leukocytes in vivo.

Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown.

Ablation of TrkA function in the immune system causes B cell abnormalities.

The nerve growth factor (NGF) receptor TrkA is widely expressed in non-neural tissues suggesting pleiotropic functions outside the nervous system. Based on pharmacological and immuno-depletion experiments, it has been hypothesized that NGF plays an important role in the normal development and function of the immune system. However, attempts to unravel these functions by conventional gene targeting in mice have been hampered by the early postnatal lethality caused by null mutations.