Peer-Reviewed Journal Details
Mandatory Fields
Hegarty, SV;Collins, LM;Gavin, AM;Roche, SL;Wyatt, SL;Sullivan, AM;O'Keeffe, GW
2014
June
Neuromolecular medicine
Canonical BMP-Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons
Validated
WOS: 35 ()
Optional Fields
GROWTH/DIFFERENTIATION FACTOR 5 BONE MORPHOGENETIC PROTEINS CENTRAL-NERVOUS-SYSTEM IMMUNO-CYTOCHEMICAL LOCALIZATION DEVELOPMENTAL CELL-DEATH DORSAL SPINAL-CORD PARKINSONS-DISEASE NEUROTROPHIC FACTOR SUBSTANTIA-NIGRA TYROSINE-HYDROXYLASE
16
473
489
Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum via the nigrostriatal pathway to regulate voluntary movements, and their loss leads to the motor dysfunction seen in Parkinson's disease (PD). Despite recent progress in the understanding of VM DA neurogenesis, the factors regulating nigrostriatal pathway development remain largely unknown. The bone morphogenetic protein (BMP) family regulates neurite growth in the developing nervous system and may contribute to nigrostriatal pathway development. Two related members of this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic effects, including promotion of neurite growth, on cultured VM DA neurons. However, the molecular mechanisms regulating their effects on DA neurons are unknown. By characterising the temporal expression profiles of endogenous BMP receptors (BMPRs) in the developing and adult rat VM and striatum, this study identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad plasmids, this study demonstrated that GDF5- and BMP2-induced neurite outgrowth from cultured VM DA neurons is dependent on BMP type I receptor activation of the Smad 1/5/8 signalling pathway.
TOTOWA
1535-1084
10.1007/s12017-014-8299-5
Grant Details