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Canonical BMP–Smad signalling promotes neurite growth in rat midbrain dopaminergic neurons

Hegarty, Shane V., Collins, Louise M., Gavin, Aisling M., Roche, Sarah L., Wyatt, Sean Lee, Sullivan, Aideen M. and O'Keeffe, Gerard W. 2014. Canonical BMP–Smad signalling promotes neurite growth in rat midbrain dopaminergic neurons. NeuroMolecular Medicine 16 (2) , pp. 473-489. 10.1007/s12017-014-8299-5

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: BMP2; GDF5; Ventral midbrain; Dopaminergic neurons; Neurite growth BMP receptor Smad signalling
Publisher: Springer
ISSN: 1559-1174
Last Modified: 18 Feb 2019 16:36
URI: http://orca.cf.ac.uk/id/eprint/60157

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