Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure

Hamblet, Natasha S.; Lijam, Nardos; Ruiz‐Lozano, Pilar; Wang, Jianbo; Ye, Yang; Luo, Zhen-Ge; Mei, Lin; Chien, Kenneth R.; Sussman, Daniel L.; Wynshaw‐Boris, Anthony

doi:10.1242/dev.00164

Cited by 404 publications

(338 citation statements)

References 66 publications

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“…The Fz3 mutation on a 129/SVJ x C57BL6 background shows a small percentage of exencephaly, which appears to be dependent on modifiers . Embryos deficient in Dvl2 show a low percentage of exencephaly and spina bifida, whereas most Dvl1 À/À ; Dvl2 À/À double mutants show craniorachischisis on a 129SvEv inbred strain and a mixed 129SvEv x NIH Black Swiss strain (Hamblet et al, 2002). Other combined mutations have also shown a percentage of exencephaly, including Dvl3 6 ; Vangl2 Lpþ (5 cranio, 2 exen /22), whereas Dvl3 À/À ; Vangl2 Lp/þ showed only craniorachischisis (6/16) on a mixed genetic background with 129S6 (Etheridge et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…PCP has also been implicated in the cell movements that form the eyelid (Murdoch et al, 2001;Wang and Nathans, 2007). Defects in PCP genes constitute approximately 5% of all known murine NTD mutations and are usually associated with craniorachischisis (a lack of neural tube closure throughout its length), open eyelids, and rotational defects of the cochlear sensory cells (Kibar et al, 2001;Murdoch et al, 2001;Hamblet et al, 2002;Curtin et al, 2003;Montcouquiol et al, 2003;Lu et al, 2004;Wang et al, 2006b;Harris and Juriloff, 2007;Torban et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Dawe

Kooistra

Fairbridge

et al. 2011

Developmental Dynamics

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The loss of Cecr2, which encodes a chromatin remodeling protein, has been associated with the neural tube defect (NTD) exencephaly and open eyelids in mice. Here, we show that two independent mutations of Cecr2 are also associated with specific inner ear defects. Homozygous mutant 18.5 days post coitus (dpc) fetuses exhibited smaller cochleae as well as rotational defects of sensory cells and extra cell rows in the inner ear reminiscent of planar cell polarity (PCP) mutants. Cecr2 was expressed in the neuroepithelium, head mesenchyme, and the cochlear floor. Although limited genetic interaction for NTDs was seen with Vangl2, a microarray analysis of PCP genes did not reveal a direct connection to this pathway. The mechanism of Cecr2 action in neurogenesis and inner ear development is likely complex.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Dawe

Kooistra

Fairbridge

et al. 2011

Developmental Dynamics

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“…Instead, Pnn hypomorphs exhibited a complex phenotype. Intriguingly, all of these phenotypes-vertebral patterning (Ikeya and Takada, 2001;Aulehla et al, 2003), dorsal dermis development (Olivera-Martinez et al, 2001, BAT formation (Atit et al, 2006), and palate and outflow tract development (Hamblet et al, 2002;Hutson and Kirby, 2003;Schmidt and Patel, 2005)-have been observed in mice having defects in Wnt/␤-catenin signaling. This finding raised an interesting possibility that PNN might be involved in the regulation of Wnt/␤-catenin signaling during mouse development.…”

Section: Discussionmentioning

confidence: 99%

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Joo

Lee

Munguba

et al. 2007

Developmental Dynamics

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Previous in vitro studies have indicated multiple and varied roles of Pinin (PNN); however, its in vivo role has remained unclear. Here, we report generation of null, hypomorphic, and conditional Pnn alleles in mice. We found that insertion of neomycin-resistance cassette into intron 8 of Pnn resulted in knockdown of Pnn, which allowed Pnn hypomorphic embryos to pass peri-implantation lethality. These mice are lethal at perinatal stages and exhibit defects in the cardiac outflow tract, palate, dorsal dermis, and axial skeleton. Since Wnt/␤-catenin signaling has been shown to play pivotal roles in development of all tissues affected by Pnn hypomorphism, we speculated that Pnn may affect Wnt/␤-catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in ␤-catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pnn plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity. Developmental Dynamics 236: 2147-2158, 2007.

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“…Embryos positive for Math1/GFP or Math1-RFP were identified by positive GFP or RFP signals in the cerebellum and spinal cord, respectively. Genotyping for Dvl1, Dvl2 knockout alleles, and the Looptail allele was carried out as described 16,[19][20] . To differentiate the Dvl2-EGFP BAC transgene from the endogenous wild-type Dvl2, a pair of primers flanking intron 2 were used for PCR (supplemental Table II).…”

Section: Mouse Strains and Animal Carementioning

confidence: 99%

Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway

et al. 2005

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The mammalian auditory sensory organ, the organ of Corti, consists of sensory hair cells with uniformly oriented stereocilia on the apical surfaces, displaying a distinct planar cell polarity (PCP) parallel to the sensory epithelium 1-3 . It is not clear how this polarity is achieved during differentiation 4-5 . Here we show that the organ of Corti is formed from a thicker and shorter postmitotic primordium through unidirectional extension, characteristic of cellular intercalation known as convergent extension 6 . Mutations in the PCP pathway interfere with this extension, resulting a shortened and widened cochlea, as well as misorientation of stereocilia. Furthermore, parallel to the homologous pathway in Drosophila 7,8 , a mammalian PCP component Dishevelled2 displays PCPdependent polarized subcellular localization across the organ of Corti. Together, these data suggest a conserved molecular mechanism for PCP pathways in invertebrates and vertebrates, and indicate that the mammalian PCP pathway might directly couple cellular intercalations to PCP establishment in the cochlea.Between embryonic day 13 (E13) and E14, precursors for the organ of Corti can be identified as a zone of non-proliferating cells within the cochlear duct using BrdU pulse-labeling (Fig. 1c, brackets) 4,9-10 . Subsequently, a gradient of cell differentiation within the precursor domain initiates near the base of the cochlea and leads to the patterning of one row of inner and three rows of outer hair cells (Fig. 1d , 1e) along the entire length of the cochlea by E18.5 10 , with uniformly oriented stereocilia on the apical surface of hair cells (Fig. 1e, green). From E14.5 to E18.5, the length of the cochlea is increased approximately 2 fold ( Fig. 1a-b). As viewed in cross sections, the developing organ of Corti in the same period is thinned from a 4-5 cell layered primordium (Fig. 1g) to only two layers of cells (Fig. 1h). One layer of hair cells lies above a layer of supporting cell nuclei whose cytoplasmic phalangeal processes reach the apexes of the hair cells, separating them from each other (Fig. 1h). Based on these observations, we have previously proposed that the longer and thinner mature organ is formed from a defined number of postmitotic precursor cells through integrated cellular intercalation movements 4 . BrdU chasing from E14 to E18 further indicated that there was no detectable cell mixing between the primordial organ of Corti and the surrounding cells (Fig. 1d) the hair cells at E14.5 marked by red fluorescent protein (Math1/RFP) were multi-cell layered ( Fig. 1f) within the sensory primordium (Fig. 1g). The thinning of the sensory primordium is accomplished by E18.5 without detectable cell death ( Fig. 1g-h).To further test our hypothesis, we bisected E14.5 cochlear epithelia into apical and basal portions, cultured them in a defined media. Using the cutting wound sites as reference points, we monitored the extension of the organ of Corti from apical-to-basal or basal-to-apical directions for the apical cultures ...

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Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure

Cited by 404 publications

References 66 publications

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway

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