2003
DOI: 10.1073/pnas.1534900100
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Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a

Abstract: The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that ␤-catenin is expressed in DA precursor cells and that ␤-catenin signaling takes place in these cells, as assessed in TOPGAL [Tcf optimal-promoter ␤-galactosidase] reporter mice. We also found that Wnt-1, -3a, and -5a expression is differentially regulated durin… Show more

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Cited by 337 publications
(363 citation statements)
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“…In keeping with this, Wnt1/5a double KO (DKO) mice show exacerbated loss of dopaminergic neurons, when compared to Wnt5a KO mice, as described by Andersson et al [52]. This elegant study also showed that mouse stem cells treated with both Wnt-3a and Wnt-5a produced more dopaminergic neurons, than cells treated with a single Wnt, providing further evidence for cooperation between noncanonical and canonical Wnts during dopaminergic differentiation, as suggested in an earlier study by the same group [53].…”
Section: Wnt Signaling In the Mouse Brain: Wnt Ligands And Receptorssupporting
confidence: 74%
“…In keeping with this, Wnt1/5a double KO (DKO) mice show exacerbated loss of dopaminergic neurons, when compared to Wnt5a KO mice, as described by Andersson et al [52]. This elegant study also showed that mouse stem cells treated with both Wnt-3a and Wnt-5a produced more dopaminergic neurons, than cells treated with a single Wnt, providing further evidence for cooperation between noncanonical and canonical Wnts during dopaminergic differentiation, as suggested in an earlier study by the same group [53].…”
Section: Wnt Signaling In the Mouse Brain: Wnt Ligands And Receptorssupporting
confidence: 74%
“…Indeed, although they are not classical neurotrophic factors, both sets of genes are critical for normal brain development [16,98] and specifically control the architectural development of the hippocampus and neocortex [32,52,54,70,100], two areas that are known to be targeted for disruption by organophosphates [1,65,72,73,91]. There is limited information linking altered expression of specific members of the wnt and fzd families to adverse neurobehavioral outcomes, but it is notable that wnt5a and fzd3, which we found to be reduced by both chlorpyrifos and diazinon, are key determinants in establishing the dopaminergic phenotype [12] and development of dopamine projections [96]. Here again, our results provide strong evidence for parallel or interactive participation of the wnt and fzd pathways with the fgf family, since we previously identified suppression of fgf members associated with the ontogeny of dopamine systems [79], which are especially sensitive to chlorpyrifos [3,25,76,78,80], and which likely underlie the association of organophosphate exposure with the subsequent development of Parkinson's Disease [43,47].…”
Section: Discussionmentioning
confidence: 71%
“…Coincubation of neurospheres with Sildenafil and LY 294002, a pharmacological inhibitor of PI3-K/Akt, abolished Sildenafil-induced phosphorylated Akt and GSK-3, indicating that Sildenafil can functionally activate downstream targets of PI3-K such as Akt and GSK-3. Glycogen synthase kinase 3 is an important component of Wnt signaling, which regulates neurogenesis during development (Castelo-Branco et al, 2003). Furthermore, LY 294002 blocked Sildenafil-increased SVZ cell proliferation.…”
Section: Discussionmentioning
confidence: 98%