Cell-cell communication represents the combined effects of multiple polypeptide factors. To explain complex effects in the nervous system requires an understanding of how local circuits and signal transduction pathways are integrated. Ephrins and Neurotrophins display both rapid and slower long lasting effects that require receptor signaling to proceed in a linear stop-wise fashion, but also influence each other, either directly or through signaling intermediates. Regulation of Ephrins and Neurotrophins is likely to be determined by the additive effects of their receptors and the duration of second messengers and phosphorylation events. Interactions between Ephrin and Neurotrophin receptors and downstream signaling proteins provide a mechanism for merging the actions of different ligand-receptor systems in order to achieve novel cellular outcomes. This subproject will focus on a set of downstream substrates that are used by both Ephrin and Neurotrophin receptors. The hypothesis is that cooperativity and antagonism between these two different transmembrane protein systems provide additional mechanisms for extracellular signaling. The proposed research is relevant to the understanding and treatment of early developmental disorders, such as autism, and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis, which depend upon the actions of Ephrins and Neurotrophins for correct developmental patterning and circuit formation.

Public Health Relevance

Ephrins and Neurotrophlns represent major polypeptide factors that influence many aspects of the nervous system, including growth cone guidance, axonal growth and higher order activities, such as synaptic plasticity. BDNF and ephrins are involved in synapse modification and hippocampal neural activity. The study of the combined effects of neurotrophins and ephrins will help to understand their roles during development and degenerative diseases, such as Alzheimer's disease and spinal cord injury.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (DC))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rbhs-Robert Wood Johnson Medical School
United States
Zip Code
Deinhardt, Katrin; Chao, Moses V (2014) Shaping neurons: Long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology 76 Pt C:603-9
Yang, Jianmin; Harte-Hargrove, Lauren C; Siao, Chia-Jen et al. (2014) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep 7:796-806
Fulmer, Clifton G; VonDran, Melissa W; Stillman, Althea A et al. (2014) Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination. J Neurosci 34:8186-96
Bowling, Heather; Zhang, Guoan; Bhattacharya, Aditi et al. (2014) Antipsychotics activate mTORC1-dependent translation to enhance neuronal morphological complexity. Sci Signal 7:ra4
Sheleg, Michal; Yochum, Carrie L; Wagner, George C et al. (2013) Ephrin-A5 deficiency alters sensorimotor and monoaminergic development. Behav Brain Res 236:139-47
Das, Gitanjali; Reuhl, Kenneth; Zhou, Renping (2013) The Golgi-Cox method. Methods Mol Biol 1018:313-21
Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V et al. (2013) Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction. Nat Commun 4:2490
Lee, Chi Wai; Vitriol, Eric A; Shim, Sangwoo et al. (2013) Dynamic localization of G-actin during membrane protrusion in neuronal motility. Curr Biol 23:1046-56
Huang, Yangyang; Dreyfus, Cheryl F (2013) Culturing astrocytes from postnatal rats. Methods Mol Biol 1018:71-80
Rui, Yanfang; Myers, Kenneth R; Yu, Kuai et al. (2013) Activity-dependent regulation of dendritic growth and maintenance by glycogen synthase kinase 3*. Nat Commun 4:2628

Showing the most recent 10 out of 172 publications