Manipulating gene activity in Wnt1‐expressing precursors of neural epithelial and neural crest cells

Hsu, Wei-Hsuan; Mirando, Anthony J.; Yu, Hsiao-Man Ivy

doi:10.1002/dvdy.22044

Cited by 21 publications

(26 citation statements)

References 38 publications

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“…To determine the in vivo functions of RhoA in neural progenitors, we generated RhoA-floxed mice (Fig. S1) and crossed them with Wnt1-Cre mice that express Cre recombinase in the mesencephalon as well as in neural crest derivatives (23). By crossing with stop-floxed EGFP reporter mice, we detected the Wnt1-Cre-mediated Cre/loxP recombination in the mesencephalon at E9.5 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation

Katayama

Meléndez

Baumann

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

138

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The organization of neural progenitors in the developing mammalian neuroepithelium is marked by cadherin-based adherens junctions. Whereas RhoA, a founding member of the small Rho GTPase family, has been shown to play important roles in epithelial adherens junctions, its physiological roles in neural development remain uncertain due to the lack of specific loss-of-function studies. Here, we show that RhoA protein accumulates at adherens junctions in the developing mouse brain and colocalizes to the cadherin–catenin complex. Conditional deletion of RhoA in midbrain and forebrain neural progenitors using Wnt1-Cre and Foxg1-Cre mice, respectively, disrupts apical adherens junctions and causes massive dysplasia of the brain. Furthermore, RhoA -deficient neural progenitor cells exhibit accelerated proliferation, reduction of cell- cycle exit, and increased expression of downstream target genes of the hedgehog pathway. Consequently, both lines of conditional RhoA -deficient embryos exhibit expansion of neural progenitor cells and exencephaly-like protrusions. These results demonstrate a critical role of RhoA in the maintenance of apical adherens junctions and the regulation of neural progenitor proliferation in the developing mammalian brain.

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Section: Resultsmentioning

confidence: 99%

Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation

Katayama

Meléndez

Baumann

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

138

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“…RNA probes (5,25) were generated to analyze the gene expression pattern by in situ hybridization (45). Histology, ␤-gal staining, immunostaining, immunoblot, protein precipitation, chromatin immunoprecipitation, and various DNA vectors used are described in the SI Methods (39,40,42,(45)(46)(47).…”

Section: Methodsmentioning

confidence: 99%

Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation

Jiang

Mirando

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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192

257

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Members of the Wnt family are secreted glycoproteins that trigger cellular signals essential for proper development of organisms. Cellular signaling induced by Wnt proteins is involved in diverse developmental processes and human diseases. Previous studies have generated an enormous wealth of knowledge on the events in signal-receiving cells. However, relatively little is known about the making of Wnt in signal-producing cells. Here, we describe that Gpr177, the mouse orthologue of Drosophila Wls, is expressed during formation of embryonic axes. Embryos with deficient Gpr177 exhibit defects in establishment of the body axis, a phenotype highly reminiscent to the loss of Wnt3. Although many different mammalian Wnt proteins are required for a wide range of developmental processes, the Wnt3 ablation exhibits the earliest developmental abnormality. This suggests that the Gpr177-mediated Wnt production cannot be substituted. As a direct target of Wnt, Gpr177 is activated by ␤-catenin and LEF/TCF-dependent transcription. This activation alters the cellular distributions of Gpr177 which binds to Wnt proteins and assists their sorting and secretion in a feedback regulatory mechanism. Our findings demonstrate that the loss of Gpr177 affects Wnt production in the signal-producing cells, leading to alterations of Wnt signaling in the signal-receiving cells. A reciprocal regulation of Wnt and Gpr177 is essential for the patterning of the anterior-posterior axis during mammalian development.A-P axis ͉ ␤-catenin ͉ developmental deformities ͉ primitive streak ͉ Wnt production

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“…For generating the Axin2 GFP mouse strain (32), mice carrying the Axin2-rtTA and TRE-H2BGFP transgenes were obtained and treated with doxycycline (2 mg/ml plus 50 mg/ml sucrose) for 7 days as described (33, 48, 52). For generating the sβcat Ax2 mouse strain, mice carrying Axin2-rtTA and TRE-Cre transgenes were first bred into the β-catΔEx3Fx heterozygous background.…”

Section: Methodsmentioning

confidence: 99%

The Balance of WNT and FGF Signaling Influences Mesenchymal Stem Cell Fate During Skeletal Development

et al. 2010

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Craniosynostosis, a developmental disorder resulting from premature closure of the gaps (sutures) between skull bones, can be caused by excessive intramembranous ossification, a type of bone formation that does not involve formation of a cartilage template (chondrogenesis). Here, we show that endochondral ossification, a type of bone formation that proceeds through a cartilage intermediate, caused by switching the fate of mesenchymal stem cells to chondrocytes, can also result in craniosynostosis. Simultaneous knockout of Axin2, a negative regulator of the WNT-β-catenin pathway, and decreased activity of fibroblast growth factor (FGF) receptor 1 (FGFR1) in mice induced ectopic chondrogenesis, leading to abnormal suture morphogenesis and fusion. Genetic analyses revealed that activation of β-catenin cooperated with FGFR1 to alter the lineage commitment of mesenchymal stem cells to differentiate into chondrocytes, from which cartilage is formed. We showed that the WNT-β-catenin pathway directly controlled the stem cell population by regulating its renewal and proliferation, and indirectly modulated lineage specification by setting the balance of the FGF and bone morphogenetic protein pathways. This study identifies endochondral ossification as a mechanism of suture closure during development and implicates this process in craniosynostosis.

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Manipulating gene activity in Wnt1‐expressing precursors of neural epithelial and neural crest cells

Cited by 21 publications

References 38 publications

Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation

Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation

Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation

The Balance of WNT and FGF Signaling Influences Mesenchymal Stem Cell Fate During Skeletal Development

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