The derivatives of the <i>Wnt3a</i> lineage in the central nervous system

Louvi, Angeliki; Yoshida, Michio; Grove, Elizabeth A.

doi:10.1002/cne.21461

Cited by 71 publications

(76 citation statements)

References 106 publications

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“…Finally, a previous report using genetic fate mapping has demonstrated that the Wnt3a cell lineage contributes to diverse structures in the diencephalon, midbrain, and spinal cord (Louvi et al, 2007). Wnt3a expression was mapped in the entire dorsal thalamic epithelium and mantle layer (Louvi et al, 2007). However, we found that Wnt3a expression was strongly reduced in Fgf8 neo /neo and almost abolished in Fgf8 null /neo mutants, with only a narrow expression domain restricted to the dorsal midline epithelium remaining ( Fig.…”

Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 47%

“…4 E, F ). Finally, a previous report using genetic fate mapping has demonstrated that the Wnt3a cell lineage contributes to diverse structures in the diencephalon, midbrain, and spinal cord (Louvi et al, 2007). Wnt3a expression was mapped in the entire dorsal thalamic epithelium and mantle layer (Louvi et al, 2007).…”

Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 96%

“…4G-I ). This dose-dependent phenotype and the possible importance of the Wnt3a expression pattern in developing thalamic nuclei (Louvi et al, 2007) motivated us to carefully examine whether Wnt3a expression is Fgf8 dependent. Thus, we analyzed the expression of Wnt3a in mouse neuroepithelial culture explants, in which recombinant Fgf8-soaked beads were inserted to perform gain-of-function experiments.…”

Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 99%

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The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

Martínez-Ferre¹,

Martı́nez²

2009

J. Neurosci.

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Habenular nuclei play a key role in the control of motor and cognitive behavior, processing emotion, motivation, and reward values in the brain. Thus, analysis of the molecular and cellular mechanisms underlying the development and evolution of this region will contribute to a better understanding of brain function. The Fgf8 gene is expressed in the dorsal midline of the diencephalon, close to the area in which the habenular region will develop. Given that Fgf8 is an important morphogenetic signal, we decided to investigate the role of Fgf8 signaling in diencephalic development. To this end, we analyzed the effects of altered Fgf8 expression in the mouse embryo, using molecular and cellular markers. Decreasing Fgf8 activity in the diencephalon was found to be associated with dosage-dependent alterations in the epithalamus: the habenular region and pineal gland are reduced or lacking in Fgf8 hypomorphic mice. Actually, our findings indicate that Fgf8 may be the master gene for these diencephalic domains, acting as an inductive and morphogenetic regulator. Therefore, the emergence of the habenular region in vertebrates could be understood in terms of a phylogenetic territorial addition caused by de novo expression of Fgf8 in the diencephalic alar plate. This region specializes to permit the development of adaptive control of the motor function in the vertebrate brain.

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Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 47%

Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 96%

Section: Wnt1 Wnt3a and Bmp4 Expression Is Altered In Fgf8 Hypomorpmentioning

confidence: 99%

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The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

Martínez-Ferre¹,

Martı́nez²

2009

J. Neurosci.

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“…Thus, early Wnt signaling is crucial for establishing thalamic identity and forming the ZLI. Wnt ligands are induced within the caudal forebrain itself shortly before ZLI formation and they are still expressed within and near the thalamus during neurogenesis (Salinas and Nusse, 1992;Bulfone et al, 1993;Louvi et al, 2007; Quinlan et RESEARCH ARTICLE -Catenin signaling patterns the thalamus al., 2009). Wnt ligands and their downstream transcription factors Lef1 and Tcf4 are expressed in unique patterns within the embryonic mouse thalamus and/or the ZLI and transcriptional activity of a target gene, Axin2, is differential within the thalamus .…”

Section: Introductionmentioning

confidence: 99%

β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus

et al. 2012

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SUMMARYNeural progenitor cells within the developing thalamus are spatially organized into distinct populations. Their correct specification is critical for generating appropriate neuronal subtypes in specific locations during development. Secreted signaling molecules, such as sonic hedgehog (Shh) and Wnts, are required for the initial formation of the thalamic primordium. Once thalamic identity is established and neurogenesis is initiated, Shh regulates the positional identity of thalamic progenitor cells. Although Wnt/-catenin signaling also has differential activity within the thalamus during this stage of development, its significance has not been directly addressed. In this study, we used conditional gene manipulations in mice and explored the roles of -catenin signaling in the regional identity of thalamic progenitor cells. We found -catenin is required during thalamic neurogenesis to maintain thalamic fate while suppressing prethalamic fate, demonstrating that regulation of regional fate continues to require extrinsic signals. These roles of -catenin appeared to be mediated at least partly by regulating two basic helix-loop-helix (bHLH) transcription factors, Neurog1 and Neurog2. -Catenin and Shh signaling function in parallel to specify two progenitor domains within the thalamus, where individual transcription factors expressed in each progenitor domain were regulated differently by the two signaling pathways. We conclude that -catenin has multiple functions during thalamic neurogenesis and that both Shh and -catenin pathways are important for specifying distinct types of thalamic progenitor cells, ensuring that the appropriate neuronal subtypes are generated in the correct locations.

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“…The dorsal thalamus is a unique part of the brain with regard to the prevalence of Wnt pathway components during organogenesis and in adulthood. Thalamic neurons originate in WNT3A cell lineage, which extensively migrate from the dorsal midline of the neural tube and populate the dorsal half of the adult brain (16). The activity of the Wnt pathway is indispensable for dorsal thalamus primordia because the thalamus is totally disorganized in mice with a mutation in LRP6 (17).…”

mentioning

confidence: 99%

WNT Protein-independent Constitutive Nuclear Localization of β-Catenin Protein and Its Low Degradation Rate in Thalamic Neurons

Misztal

Wisniewska

Ambrozkiewicz

et al. 2011

Journal of Biological Chemistry

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Nuclear localization of ␤-catenin is a hallmark of canonical Wnt signaling, a pathway that plays a crucial role in brain development and the neurogenesis of the adult brain. We recently showed that ␤-catenin accumulates specifically in mature thalamic neurons, where it regulates the expression of the Ca v 3.1 voltage-gated calcium channel gene. Here, we investigated the mechanisms underlying ␤-catenin accumulation in thalamic neurons. We report that a lack of soluble factors produced either by glia or cortical neurons does not impair nuclear ␤-catenin accumulation in thalamic neurons. We next found that the number of thalamic neurons with ␤-catenin nuclear localization did not change when the Wnt/Dishevelled signaling pathway was inhibited by Dickkopf1 or a dominant negative mutant of Dishevelled3. These results suggest a WNT-independent cellautonomous mechanism. We found that the protein levels of APC, AXIN1, and GSK3␤, components of the ␤-catenin degradation complex, were lower in the thalamus than in the cortex of the adult rat brain. Reduced levels of these proteins were also observed in cultured thalamic neurons compared with cortical cultures. Finally, pulse-chase experiments confirmed that cytoplasmic ␤-catenin turnover was slower in thalamic neurons than in cortical neurons. Altogether, our data indicate that the nuclear localization of ␤-catenin in thalamic neurons is their cell-intrinsic feature, which was WNT-independent but associated with low levels of proteins involved in ␤-catenin labeling for ubiquitination and subsequent degradation.

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The derivatives of the Wnt3a lineage in the central nervous system

Cited by 71 publications

References 106 publications

The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus

WNT Protein-independent Constitutive Nuclear Localization of β-Catenin Protein and Its Low Degradation Rate in Thalamic Neurons

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