Molecular Neurobiology

, Volume 50, Issue 2, pp 559–573

Roles for the TGFβ Superfamily in the Development and Survival of Midbrain Dopaminergic Neurons

Article

DOI: 10.1007/s12035-014-8639-3

Cite this article as:
Hegarty, S.V., Sullivan, A.M. & O’Keeffe, G.W. Mol Neurobiol (2014) 50: 559. doi:10.1007/s12035-014-8639-3

Abstract

The adult midbrain contains 75 % of all dopaminergic neurons in the CNS. Within the midbrain, these neurons are divided into three anatomically and functionally distinct clusters termed A8, A9 and A10. The A9 group plays a functionally non-redundant role in the control of voluntary movement, which is highlighted by the motor syndrome that results from their progressive degeneration in the neurodegenerative disorder, Parkinson’s disease. Despite 50 years of investigation, treatment for Parkinson’s disease remains symptomatic, but an intensive research effort has proposed delivering neurotrophic factors to the brain to protect the remaining dopaminergic neurons, or using these neurotrophic factors to differentiate dopaminergic neurons from stem cell sources for cell transplantation. Most neurotrophic factors studied in this context have been members of the transforming growth factor β (TGFβ) superfamily. In recent years, an intensive research effort has focused on understanding the function of these proteins in midbrain dopaminergic neuron development and their role in the molecular architecture that regulates the development of this brain region, with the goal of applying this knowledge to develop novel therapies for Parkinson’s disease. In this review, the current evidence showing that TGFβ superfamily members play critical roles in the regulation of midbrain dopaminergic neuron induction, differentiation, target innervation and survival during embryonic and postnatal development is analysed, and the implications of these findings are discussed.

Keywords

TGFβ superfamily BMP family Midbrain dopaminergic neurons Development Neurogenesis 

Abbreviations

6-OHDA

6-Hydroxydopamine

ALK

Activin receptor-like kinases

BDNF

Brain-derived neurotrophic factor

BMP

Bone morphogenetic protein

BMPR

BMP receptors

Co-Smads

Common mediator Smads

DA

Dopaminergic/dopamine

E

Embryonic day

FGF

Fibroblast growth factor

GDF

Growth/differentiation factor

GDNF

Glial cell line-derived neurotrophic factor

I-Smads

Inhibitory Smads

MPP+

1-Methyl-4-phenylpyridinium ion

P

Postnatal day

PD

Parkinson’s disease

R-Smads

Receptor-regulated Smads

Shh

Sonic hedgehog

TGFβ

Transforming growth factor β

TH

Tyrosine hydroxylase

VM

Ventral midbrain/mesencephalon

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Anatomy and Neuroscience, Biosciences InstituteUniversity College CorkCorkIreland

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