The central objective of this program project is to define integrative principles governing the diverse processes of brain development. We hypothesize that reciprocal neuron-neuron and neuron-glial-neuron interactions, mediated by a limited set of intercellular signals, coordinate seemingly unrelated developmental events. Specifically, (a) trophic factors, including the diffusible neurotrophin gene family members, b) growth (mitogenic) factors, including bFGF, c) membrane-bound, chemorepulsive, cellular labels of the Eph gene family, and d) conventional neurotransmitters working combinatorially, synchronize the developmental sequence. These molecular signals coordinate neuronal mitosis, selective survival, axogenesis, pathfinding, topographic projection and synaptic plasticity. The epigenetic molecular signals mediate and integrate neural activity, trophic and glial coordination of proliferation, selective survival, pathway formation and synaptic function. We will employ multidisciplinary molecular genetic, biochemical and morphologic approaches to study neuronal development in vivo and in culture. We plan to define a) neuroblasts, b) the role of peripheral bFGF in brain neurogenesis, c) the role of the p75 neurotrophin receptor in developmental cell death and survival, d) the role of Eph family ligands and receptors in brain topographic projection, e) trophic regulation of synaptic plasticity and 3) the role of astrocyte-neuron interactions in brain development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD023315-12
Application #
2888951
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (IB))
Project Start
1987-07-01
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Neurosciences
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Sheleg, M; Yu, Q; Go, C et al. (2017) Decreased maternal behavior and anxiety in ephrin-A5-/- mice. Genes Brain Behav 16:271-284
Bowling, Heather; Bhattacharya, Aditi; Klann, Eric et al. (2016) Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology. Neural Regen Res 11:363-7
Huang, Yangyang; Dreyfus, Cheryl F (2016) The role of growth factors as a therapeutic approach to demyelinating disease. Exp Neurol 283:531-40
Lee, Hee Jae; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel (2016) Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat. Dev Neurobiol 76:780-98
Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan et al. (2016) BONLAC: A combinatorial proteomic technique to measure stimulus-induced translational profiles in brain slices. Neuropharmacology 100:76-89
Mony, Tamanna Jahan; Lee, Jae Won; Dreyfus, Cheryl et al. (2016) Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats. Clin Psychopharmacol Neurosci 14:338-344
Das, Gitanjali; Yu, Qili; Hui, Ryan et al. (2016) EphA5 and EphA6: regulation of neuronal and spine morphology. Cell Biosci 6:48
Ma, Qian; Yang, Jianmin; Li, Thomas et al. (2015) Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease. Neurobiol Dis 82:466-477
Anastasia, Agustin; Barker, Phillip A; Chao, Moses V et al. (2015) Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation. J Neurosci 35:11911-20
Sheleg, Michal; Yochum, Carrie L; Richardson, Jason R et al. (2015) Ephrin-A5 regulates inter-male aggression in mice. Behav Brain Res 286:300-7

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