Genetic susceptibility in the neural tube defects induced by ochratoxin A in the genetic arhinencephaly mouse,<i>Pdn/Pdn</i>

Ohta, Kenichi; Maekawa, Mizuho; Katagiri, Ryuichi; Ueta, Etsuko

doi:10.1111/j.1741-4520.2006.00117.x

Cited by 11 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…No ectopic and/or over-expression of Shh was detected in the Gli3 depressed Pdn/Pdn embryos (Figs 2; 3B; 4H). It was reported that Shh is upstream of Gli3 in the signaling pathway (Ming et al 1998), and that depression of Gli3 expression does not affect to Shh expression (Aoto et al 2002;Lamm et al 2002;te-Welscher et al 2002;Altaba et al 2003;Kuschel et al 2003;Ohta et al 2006), being consistent with the present data (Figs 2; 3B; 4H). Gli3 mutants exhibit an expansion of Fgf8 expression ( Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Real-time PCR method has been described previously (Ohta et al 2006;Katagiri et al 2007). After removing the yolk sac membrane for genotyping, the head region of six embryos in both +/+ and Pdn/Pdn on day 9 of gestation were collected and frozen in liquid nitrogen and total RNA was isolated using the RNeasy Mini Kit (QIAGEN, Tokyo, Japan).…”

Section: Real-time Pcrmentioning

confidence: 99%

“…2). As Gli3, Emx2, Wnt8b, Wnt7b, Shh and Fgf8 have been reported to have important roles on the morphogenesis of telencephalon in the previous reports (Grove et al 1998;Theil et al 1999;Aoto et al 2002;Ohta et al 2006;Katagiri et al 2007), we investigated these gene expressions in the following experiments, real-time PCR and whole-mount in situ hybridization.…”

Section: Dna Microarraymentioning

confidence: 99%

See 2 more Smart Citations

Altered signaling pathway in the dysmorphogenesis of telencephalon in theGli3depressed mouse embryo,Pdn/Pdn

Ueta

Kurome

Teshima

et al. 2008

Congenital Anomalies

Self Cite

View full text Add to dashboard Cite

The responsible gene of genetic polydactyly/arhinencephaly mouse (Pdn/Pdn) is Gli3. Pdn/Pdn exhibits absence of the olfactory bulb, suggesting telencephalic dysmorphogenesis. It has been cleared that a transposon was inserted into intron 3 of the Gli3 gene in the Pdn mouse. Adequate PCR primers in the intron 3 and transposon allowed us to discriminate +/+, Pdn/+ and Pdn/Pdn embryos. After genotyping of the Pdn embryos using genomic DNA from the yolk sac membrane, gene expressions in the embryo proper were analyzed by DNA microarray, real-time PCR and whole-mount in situ hybridization (WISH) methods. DNA microarray detected 368 depressed and 425 over-expressed genes in the Pdn/Pdn mouse embryos on day 9 of gestation. In these genes, six signaling pathway and 20 transcription factor genes were included. From these genes, we further investigated Gli3, Emx2, Wnt8b and Wnt7b gene expressions using real-time PCR and WISH, and depression of these gene expression amounts and altered expression patterns were confirmed. Although alterations of Shh and Fgf8 gene expressions were not detected in the DNA microarray, as these genes have been closed up in the telencephalic morphogenesis, we investigated these gene expressions by real-time PCR and WISH. Shh gene expression amount and pattern were not changed. Alteration of Fgf8 gene expression amount was not detected also in the real-time PCR, but altered expression pattern was detected in the Pdn/Pdn embryos by WISH. From the present data, we suggested that Emx2, Wnt8b, Wnt7b and Fgf8 are the important Gli3 signaling pathway in the morphogenesis of telencephalon.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Real-time Pcrmentioning

confidence: 99%

Section: Dna Microarraymentioning

confidence: 99%

See 1 more Smart Citation

Altered signaling pathway in the dysmorphogenesis of telencephalon in theGli3depressed mouse embryo,Pdn/Pdn

Ueta

Kurome

Teshima

et al. 2008

Congenital Anomalies

Self Cite

View full text Add to dashboard Cite

show abstract

“…A 180 bp band with etn11F and R6 was obtained in Pdn/Pdn embryos. This genotyping allowed us to analyze the alteration of gene expression in early Pdn/Pdn mouse embryos prior to morphological signs of genotype recognition (Ueta et al 2004;Maekawa et al 2005;Naruse et al 2005;Ohta et al 2006;Katagiri et al 2007;Ueta et al 2008). To determine the sex of the embryos, we used the Sry gene sequence on the Y chromosome to obtain 274 bp PCR products in the male embryos using the primers shown in Table 1.…”

Section: Genotyping Methodsmentioning

confidence: 99%

“…OTA (Sigma-Aldrich Chemie Gmbh, Steinheim, Germany) was dissolved with 0.1 M NaHCO3 in distilled water adjusted to pH 7.4 with HCl. After mating Pdn/+ females with Pdn/+ males, 2 mg/kg OTA was administered intraperitoneally to the Pdn/+ females on day 7.5 of gestation at 18.00 hours as described in a previous study (Ohta et al 2006). Fetuses on day 18 of gestation were recovered for external observations, and conceptuses on day 9 were recovered for gene expression analysis.…”

Section: Ota Treatmentmentioning

confidence: 99%

Gender‐dependent differences in the incidence of ochratoxin A‐induced neural tube defects in the Pdn/Pdn mouse

Ueta

Kodama

Sumino

et al. 2010

Congenital Anomalies

Self Cite

View full text Add to dashboard Cite

Genetic polydactyly/arhinencephaly mouse embryo, Pdn/Pdn, exhibits suppression of Gli3 gene expression. Ochratoxin A (OTA) is a teratogen that causes neural tube defects (NTD) in mice. We investigated gender-dependent differences in the incidence of NTD induced by OTA in the Pdn/Pdn mouse. After administering 2 mg/kg OTA to Pdn/+ female mice, mated with Pdn/+ males, on day 7.5 of gestation, we examined the genotypes, sex and NTD of fetuses on day 18. Non-treated Pdn/Pdn had a 15.8% risk of NTD, and all NTD fetuses were female. When Pdn/Pdn embryos were exposed to OTA, the incidence of NTD increased to 16 (51.6%) of 31 Pdn/Pdn fetuses, and 10 (71.4%) of 14 male Pdn/Pdn fetuses exhibited NTD. From these results, it was speculated that NTD in OTA-treated male Pdn/Pdn were due to the synergistic effect between depressed Gli3 and altered sex-correlated gene expression from OTA treatment. After treatment with OTA, the embryos were recovered on day 9 and gene expressions, which were correlated with Gli3, telencephalic morphogenesis, formation of gonadal anlage, and gender-dependent differentiation were investigated. From real-time polymerase chain reaction analysis results, it was suggested that the manifestation of NTD in the male OTA-treated Pdn/Pdn might be due to the complicated altered gene expressions among Gli3, Wnt7b, Wnt8b, Fez1, Barx1, Lim1, Dmrt1, Igf1, Fog2, Dax1 and Sox9, and in particular, upregulation and gender-dependent difference in Barx1 and gender-dependent difference in Sox9 gene expressions might be noteworthy findings.

show abstract

Genesis of teratogen‐induced holoprosencephaly in mice

Lipinski

Godin

O’Leary‐Moore

et al. 2010

American J of Med Genetics Pt C

View full text Add to dashboard Cite

Evidence from mechanical, teratological, and genetic experimentation demonstrates that holoprosencephaly (HPE) typically results from insult prior to the time that neural tube closure is completed and occurs as a consequence of direct or indirect insult to the rostral prechordal cells that induce the forebrain or insult to the median forebrain tissue, itself. Here, we provide an overview of normal embryonic morphogenesis during the critical window for HPE induction, focusing on the morphology and positional relationship of the developing brain and subjacent prechordal plate and prechordal mesoderm cell populations. Subsequent morphogenesis of the HPE spectrum is then examined in selected teratogenesis mouse models. The temporal profile of Sonic Hedgehog expression in rostral embryonic cell populations and evidence for direct or indirect perturbation of the Hedgehog pathway by teratogenic agents in the genesis of HPE is highlighted. Emerging opportunities based on recent insights and new techniques to further characterize the mechanisms and pathogenesis of HPE are discussed.

show abstract

Genetic susceptibility in the neural tube defects induced by ochratoxin A in the genetic arhinencephaly mouse,Pdn/Pdn

Cited by 11 publications

References 36 publications

Altered signaling pathway in the dysmorphogenesis of telencephalon in theGli3depressed mouse embryo,Pdn/Pdn

Altered signaling pathway in the dysmorphogenesis of telencephalon in theGli3depressed mouse embryo,Pdn/Pdn

Gender‐dependent differences in the incidence of ochratoxin A‐induced neural tube defects in the Pdn/Pdn mouse

Genesis of teratogen‐induced holoprosencephaly in mice

Contact Info

Product

Resources

About