Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion

Castelo‐Branco, Gonçalo; Sousa, Kyle M.; Bryja, Vı́tězslav; Pinto, Luísa; Wagner, Joseph; Arenas, Ernest

doi:10.1016/j.mcn.2005.09.014

Cited by 91 publications

(90 citation statements)

References 69 publications

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“…However, not all protocols are equally efficient. Notably, NS/PCs expanded with mitogens as monolayers (Sanchez-Pernaute et al, 2001) or neurospheres (Maciaczyk et al, 2008;Riaz et al, 2002;Ribeiro et al, 2012), or when immortalized (Castelo-Branco et al, 2006;Courtois et al, 2010;Ramos-Moreno et al, 2012;Wagner et al, 1999), have shown variable numbers and quality of DA neurons ( Fig. 5A-E), probably due to heterogeneity and/or late developmental stage of the cells and the protocols used.…”

Section: Generating Human Mda Neurons In Vitromentioning

confidence: 99%

How to make a midbrain dopaminergic neuron

2015

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Midbrain dopaminergic (mDA) neuron development has been an intense area of research during recent years. This is due in part to a growing interest in regenerative medicine and the hope that treatment for diseases affecting mDA neurons, such as Parkinson's disease (PD), might be facilitated by a better understanding of how these neurons are specified, differentiated and maintained in vivo. This knowledge might help to instruct efforts to generate mDA neurons in vitro, which holds promise not only for cell replacement therapy, but also for disease modeling and drug discovery. In this Primer, we will focus on recent developments in understanding the molecular mechanisms that regulate the development of mDA neurons in vivo, and how they have been used to generate human mDA neurons in vitro from pluripotent stem cells or from somatic cells via direct reprogramming. Current challenges and future avenues in the development of a regenerative medicine for PD will be identified and discussed.

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Section: Generating Human Mda Neurons In Vitromentioning

confidence: 99%

How to make a midbrain dopaminergic neuron

2015

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“…Therefore, we can speculate that the binding of Wnt7a to Fz7 triggers ReNcell VM cell differentiation. Wnt5a and Wnt5b regulate the proliferation and differentiation of chondrocytes [41] and Wnt5a can promote dopaminergic neurogenesis [42]. Previous studies have shown that ReNcell VM cells are inducible to differentiate into dopaminergic neurons [4,6].…”

Section: Two Different Regulation Waves Of Endogenous Wnt Signaling Mmentioning

confidence: 99%

Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation

Mazemondet¹,

Hübner

Frahm

et al. 2011

Cellular and Molecular Biology Letters

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ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.

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“…The efficiency of the silencing was assessed by western blotting or real time RT-PCR. Quantitative RT-PCR was performed as described previously (Castelo-Branco et al, 2006) The following primers were used (DNA Technology A/S, Aarhus, Denmark): CK1␣ for 5Ј-TTTGAGGAAGCTCCGGATTACAT-3Ј, CK1␣ rev 5Ј-TCGTCCAATCAAACGTG -TAGTCAT-3´, CK1␦ for 5Ј-ACATCTATCTCGGTACGGACATTG-3Ј, CK1␦ rev 5Ј-GAGGATGTTTGGTTTTGACACATTC-3Ј.…”

Section: Rna Interference and Quantitative Rt-pcrmentioning

confidence: 99%

“…We have shown that Wnt-5a -a non-canonical Wnt, classified by its inability to activate ␤-catenin (Shimizu et al, 1997) -plays a pivotal role in the ventral midbrain DN differentiation (Castelo-Branco et al, 2006;Castelo-Branco et al, 2003). To date, the underlying molecular mechanism of action of Wnt-5a and the signalling pathways activated in DN as well as in other mammalian cells is still largely unknown (Veeman et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism

Bryja

Schulte

Rawal

et al. 2007

Journal of Cell Science

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170

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Previously, we have shown that Wnt-5a strongly regulates dopaminergic neuron differentiation by inducing phosphorylation of Dishevelled (Dvl). Here, we identify additional components of the Wnt-5a-Dvl pathway in dopaminergic cells. Using in vitro gain-of-function and loss-of-function approaches, we reveal that casein kinase 1 (CK1) δ and CK1ϵ are crucial for Dvl phosphorylation by non-canonical Wnts. We show that in response to Wnt-5a, CK1ϵ binds Dvl and is subsequently phosphorylated. Moreover, in response to Wnt-5a or CK1ϵ, the distribution of Dvl changed from punctate to an even appearance within the cytoplasm. The opposite effect was induced by a CK1ϵ kinase-dead mutant or by CK1 inhibitors. As expected, Wnt-5a blocked the Wnt-3a-induced activation of β-catenin. However, both Wnt-3a and Wnt-5a activated Dvl2 by a CK1-dependent mechanism in a cooperative manner. Finally, we show that CK1 kinase activity is necessary for Wnt-5a-induced differentiation of primary dopaminergic precursors. Thus, our data identify CK1 as a component of Wnt-5a-induced signalling machinery that regulates dopaminergic differentiation, and suggest that CK1δ/ϵ-mediated phosphorylation of Dvl is a common step in both canonical and non-canonical Wnt signalling.

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Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion

Cited by 91 publications

References 69 publications

How to make a midbrain dopaminergic neuron

How to make a midbrain dopaminergic neuron

Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation

Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism

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