Canonical BMP-Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Overview

Journal Neuromolecular Med

Specialty Biochemistry

Date 2014 Apr 1

PMID 24682653

Citations 27

Authors

Shane V Hegarty

Louise M Collins

Aisling M Gavin

Sarah L Roche

Sean L Wyatt

Aideen M Sullivan

Gerard W OKeeffe

Affiliations

Soon will be listed here.

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.

Citing Articles

Human α-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing.

Morales-Prieto N, Bevans R, OMahony A, Barron A, Giles Doran C, McCarthy E Aging Cell. 2024; 23(6):e14155.

PMID: 38529808 PMC: 11296121. DOI: 10.1111/acel.14155.

Chalazonitis A, Rao M, Sulzer D NPJ Parkinsons Dis. 2022; 8(1):50.

PMID: 35459867 PMC: 9033791. DOI: 10.1038/s41531-022-00308-9.

Ligand-receptor promiscuity enables cellular addressing.

Su C, Murugan A, Linton J, Yeluri A, Bois J, Klumpe H Cell Syst. 2022; 13(5):408-425.e12.

PMID: 35421362 PMC: 10897978. DOI: 10.1016/j.cels.2022.03.001.

Growth differentiation factor 5: a neurotrophic factor with neuroprotective potential in Parkinson's disease.

Goulding S, Anantha J, Collins L, Sullivan A, OKeeffe G Neural Regen Res. 2021; 17(1):38-44.

PMID: 34100424 PMC: 8451580. DOI: 10.4103/1673-5374.314290.

Quinacrine and Niclosamide Promote Neurite Growth in Midbrain Dopaminergic Neurons Through the Canonical BMP-Smad Pathway and Protect Against Neurotoxin and α-Synuclein-Induced Neurodegeneration.

Goulding S, Levesque M, Sullivan A, Collins L, OKeeffe G Mol Neurobiol. 2021; 58(7):3405-3416.

PMID: 33713017 DOI: 10.1007/s12035-021-02351-8.

References

Halladay A, Tessarollo L, Zhou R, Wagner G . Neurochemical and behavioral deficits consequent to expression of a dominant negative EphA5 receptor. Brain Res Mol Brain Res. 2004; 123(1-2):104-11. DOI: 10.1016/j.molbrainres.2004.01.005. View

Yamashita H, Ten Dijke P, Heldin C, Miyazono K . Bone morphogenetic protein receptors. Bone. 1996; 19(6):569-74. DOI: 10.1016/s8756-3282(96)00259-1. View

Hurley F, Costello D, Sullivan A . Neuroprotective effects of delayed administration of growth/differentiation factor-5 in the partial lesion model of Parkinson's disease. Exp Neurol. 2004; 185(2):281-9. DOI: 10.1016/j.expneurol.2003.10.003. View

Boger H, Middaugh L, Huang P, Zaman V, Smith A, Hoffer B . A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra. Exp Neurol. 2006; 202(2):336-47. DOI: 10.1016/j.expneurol.2006.06.006. View

Yamauchi K, Phan K, Butler S . BMP type I receptor complexes have distinct activities mediating cell fate and axon guidance decisions. Development. 2008; 135(6):1119-28. DOI: 10.1242/dev.012989. View

Lauder J, Bloom F . Ontogeny of monoamine neurons in the locus coeruleus, Raphe nuclei and substantia nigra of the rat. I. Cell differentiation. J Comp Neurol. 1974; 155(4):469-81. DOI: 10.1002/cne.901550407. View

Oo T, Burke R . The time course of developmental cell death in phenotypically defined dopaminergic neurons of the substantia nigra. Brain Res Dev Brain Res. 1997; 98(2):191-6. DOI: 10.1016/s0165-3806(96)00173-3. View

Chizhikov V, Millen K . Roof plate-dependent patterning of the vertebrate dorsal central nervous system. Dev Biol. 2004; 277(2):287-95. DOI: 10.1016/j.ydbio.2004.10.011. View

Burke R . Postnatal developmental programmed cell death in dopamine neurons. Ann N Y Acad Sci. 2003; 991:69-79. DOI: 10.1111/j.1749-6632.2003.tb07464.x. View

10.

Phan K, Hazen V, Frendo M, Jia Z, Butler S . The bone morphogenetic protein roof plate chemorepellent regulates the rate of commissural axonal growth. J Neurosci. 2010; 30(46):15430-40. PMC: 3064494. DOI: 10.1523/JNEUROSCI.4117-10.2010. View

11.

Hedlund E, Perlmann T . Neuronal cell replacement in Parkinson's disease. J Intern Med. 2009; 266(4):358-71. DOI: 10.1111/j.1365-2796.2009.02155.x. View

12.

Sieber B, Kuzmin A, Canals J, Danielsson A, Paratcha G, Arenas E . Disruption of EphA/ephrin-a signaling in the nigrostriatal system reduces dopaminergic innervation and dissociates behavioral responses to amphetamine and cocaine. Mol Cell Neurosci. 2004; 26(3):418-28. DOI: 10.1016/j.mcn.2004.03.009. View

13.

Nakamura S, Ito Y, Shirasaki R, Murakami F . Local directional cues control growth polarity of dopaminergic axons along the rostrocaudal axis. J Neurosci. 2000; 20(11):4112-9. PMC: 6772636. View

14.

Lin L, Rao Y, Isacson O . Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neurons. Mol Cell Neurosci. 2005; 28(3):547-55. DOI: 10.1016/j.mcn.2004.11.009. View

15.

Lumsden A, Krumlauf R . Patterning the vertebrate neuraxis. Science. 1996; 274(5290):1109-15. DOI: 10.1126/science.274.5290.1109. View

16.

Lein P, Johnson M, Guo X, Rueger D, Higgins D . Osteogenic protein-1 induces dendritic growth in rat sympathetic neurons. Neuron. 1995; 15(3):597-605. DOI: 10.1016/0896-6273(95)90148-5. View

17.

Reiriz J, Espejo M, Ventura F, Ambrosio S, Alberch J . Bone morphogenetic protein-2 promotes dissociated effects on the number and differentiation of cultured ventral mesencephalic dopaminergic neurons. J Neurobiol. 1999; 38(2):161-70. View

18.

Yu P, Hong C, Sachidanandan C, Babitt J, Deng D, Hoyng S . Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2007; 4(1):33-41. PMC: 2727650. DOI: 10.1038/nchembio.2007.54. View

19.

Gratacos E, Checa N, Perez-Navarro E, Alberch J . Brain-derived neurotrophic factor (BDNF) mediates bone morphogenetic protein-2 (BMP-2) effects on cultured striatal neurones. J Neurochem. 2001; 79(4):747-55. DOI: 10.1046/j.1471-4159.2001.00570.x. View

20.

Collins L, OKeeffe G, Long-Smith C, Wyatt S, Sullivan A, Toulouse A . Mitogen-activated protein kinase phosphatase (MKP)-1 as a neuroprotective agent: promotion of the morphological development of midbrain dopaminergic neurons. Neuromolecular Med. 2013; 15(2):435-46. DOI: 10.1007/s12017-013-8230-5. View