The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons

Zihlmann, Karin B.; Ducray, Angélique; Schaller, Benoît; Huber, Adrian Thomas; Krebs, Sandra H.; Andres, Robert H.; Seiler, Rolf W.; Meyer, Morten; Widmer, HR

doi:10.1016/j.brainresbull.2004.10.012

Cited by 56 publications

(34 citation statements)

References 70 publications

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“…5C; left and middle panels). These results may reflect a neurotrophic, paracrine effect produced by GDNF released from the genetically engineered hMSCs that converts stem or progenitor cells in 3D microenvironments into dopaminergic neurons, potentially useful for the treatment of Parkinson's disease [52,53]. The total cell number was not significantly different between the groups (Fig.…”

Section: Enhanced Differentiation Of Hnscs Into Dopaminergic Neurons mentioning

confidence: 79%

Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

et al. 2015

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Section: Enhanced Differentiation Of Hnscs Into Dopaminergic Neurons mentioning

confidence: 79%

Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

et al. 2015

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“…It also acts as a trophic factor and enhances survival of sensory and sympathetic peripheral neurons (Baloh et al 1998;Jeong et al 2008). ARTN is expressed in structures of the basal ganglia (subthalamic nucleus, putamen, and substantia nigra), thalamus, and many peripheral adult human tissues (Baloh et al 1998), and it is a potent neurotrophic factor that may play an important role in the structural development and plasticity of ventral mesencephalic dopaminergic neurons (Zihlmann et al 2005). ARTN as well as neurturin and persephin are involved in processes subserving both the organization of several cortical regions during development and the functional activity and maintenance of the mature human hippocampal neurons (Quartu et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

et al. 2011

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“…It is well documented that GDNF and NTN are potent trophic factors that have potent effects on neuronal differentiation and promote survival and sprouting of ventral mesencephalic dopaminergic neurons in primary cultures and other neuronal cultures (Lin et al, 1993;Akerud et al, 1999;Baloh et al, 2000;Yan et al, 2003;Wanigasekara and Keast, 2005;Zihlmann et al, 2005). The finding in this study of a particular alternatively spliced variant of GFR␣2 inhibiting neurite outgrowth was unexpected.…”

Section: Discussionmentioning

confidence: 50%

Glial Cell Line-Derived Neurotrophic Factor and Neurturin Inhibit Neurite Outgrowth and Activate RhoA through GFRα2b, an Alternatively Spliced Isoform of GFRα2

Yoong¹,

Too²

2007

J. Neurosci.

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The glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) belong to a structurally related family of neurotrophic factors. NTN exerts its effect through a multicomponent receptor system consisting of the GDNF family receptor ␣2 (GFR␣2), RET, and/or NCAM (neural cell adhesion molecule). GFR␣2 is alternatively spliced into at least three isoforms (GFR␣2a, GFR␣2b, and GFR␣2c). It is currently unknown whether these isoforms share similar functional and biochemical properties. Using highly specific and sensitive quantitative real-time PCR, these isoforms were found to be expressed at comparable levels in various regions of the human brain. When stimulated with GDNF and NTN, both GFR␣2a and GFR␣2c, but not GFR␣2b, promoted neurite outgrowth in transfected Neuro2A cells. These isoforms showed ligand selectivity in MAPK (mitogen-activated protein kinase) [ERK1/2 (extracellular signalregulated kinase 1/2)] and Akt signaling. In addition, the GFR␣2 isoforms regulated different early-response genes when stimulated with GDNF or NTN. In coexpression studies, GFR␣2b was found to inhibit ligand-induced neurite outgrowth by GFR␣2a and GFR␣2c. Stimulation of GFR␣2b also inhibited the neurite outgrowth induced by GFR␣1a, another member of the GFR␣. Furthermore, activation of GFR␣2b inhibited neurite outgrowth induced by retinoic acid and activated RhoA. Together, these data suggest a novel paradigm for the regulation of growth factor signaling and neurite outgrowth via an inhibitory splice variant of the receptor. Thus, depending on the expressions of specific GFR␣2 receptor spliced isoforms, GDNF and NTN may promote or inhibit neurite outgrowth through the multicomponent receptor complex.

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The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons

Cited by 56 publications

References 70 publications

Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

Glial Cell Line-Derived Neurotrophic Factor and Neurturin Inhibit Neurite Outgrowth and Activate RhoA through GFRα2b, an Alternatively Spliced Isoform of GFRα2

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