Dose dependency of<i>Disp1</i>and genetic interaction between<i>Disp1</i>and other hedgehog signaling components in the mouse

Tian, Hua; Tenzen, Toyoaki; McMahon, Andrew P.

doi:10.1242/dev.01257

Cited by 25 publications

(21 citation statements)

References 61 publications

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“…C829F and Disp1 ∆2 (Caspary et al, 2002;Kawakami et al, 2002;Ma et al, 2002;Tian et al, 2004). Analysis of these alleles lead to similar general conclusion, that Disp1 is involved in Hh signaling during early embryonic development.…”

Section: Introductionmentioning

confidence: 55%

“…In 2005, the McMahon laboratory reported that a re-examination of two papers published by their group in Development Tian et al, 2005a) had revealed a duplication of Dr Tian's data in these papers. Following their analysis, the authors announced, with regret, that they must retract Tian et al (2004), and this retraction was published by Development in November 2005, along with their apology to the editors and readership of the journal (Tian et al, 2005b). With respect to the second paper (Tian et al, 2005a), the authors' review, overseen by the Committee on Professional Conduct (CPC) for the Faculty of Arts and Sciences at Harvard University, found that the principal conclusions of the paper were supported by appropriate documentation but that the documentation for Fig.…”

Section: δ2/c829fmentioning

confidence: 99%

“…) by flanking the first coding exon with DNA recognition sites (loxP) for Cre recombinase (Cre) (see Tian et al, 2004). Mice homozygous for this allele (Disp1…”

Section: ∆2cmentioning

confidence: 99%

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Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand

Tian¹,

Jeong²,

Harfe

et al. 2005

Development

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There was a reanalysis of data required to support the findings in Development 132, 133-142.We have repeated the facial analysis reported in Fig. 2 to provide the data required to support some of the original findings of this study (see Publisher's note). Our findings substantiate the original conclusions drawn from Fig. 2 of a dose-related genetic interaction between Disp1 and Shh alleles, and of the function of Disp1 within Shh-producing cells. Some differences are reported below, which might reflect slight differences in embryonic staging or increased sensitivity of the whole-mount in situ hybridization procedure here. Importantly, they do not alter the key conclusion that reducing Disp1 levels in Shh-producing cells results in a phenotype similar to that of genetically matched embryos with reduced Disp1 activity throughout the embryo. These data support the overall conclusions of the paper, and, together with other data in the same report, support a model in which the principal requirement for Disp1 activity is in Shh-producing cells. Ptch1 and Shh expression was evident in midline cell populations rostral to the optic lobes in wild-type embryos (arrows in P and U). Their expression was either markedly reduced or lost, depending on the specific combination of Disp1 and Shh alleles (Q-T and V-Y). Ptch1 and Shh expression was detected in the midbrain region (indicated by arrowheads in P and U) of all genotypes, albeit at reduced levels. Development 135, 3471-3472 (2008) ; Shh Cre/+ embryos in which Disp1 activity was specifically knocked down in Shh-producing cells have a facial phenotype with a narrowing of the face and reduction of the premaxilla. However, the length of the snout is similar to wild type and the mandibular incisors are not fused ( Fig. 2A,C,K,M). Thus, the phenotype is, as expected, generally less severe than that of the Disp1 Δ2/Δ2; Shh +/-embryos (Fig. 2B,L). The severity of the conditional phenotype is enhanced when Disp1 activity is further lowered in Disp1 Δ2C/C829F ; Shh Cre/+ mice (Fig. 2E,O) ; Shh +/-embryos (Fig. 2D,N); the tubular nasal process was shorter and the premaxillary bone was more extensive. In a proportion of the latter, truncated fused mandibles lack incisors (Fig. 2N); however, mandibular fusion was not observed in Disp1 Δ2C/C829F ; Shh Cre/+ embryos. The slightly weaker facial phenotype seen at term with each of the conditional removal combinations was evident at E10.5 when the distance between the Fgf8-expressing frontal-nasal processes is compared by whole-mount in situ hybridization (Fig. 2F-J). Variable weak midline Shh expression was observed rostral to the optic stalk in Disp1 Δ2/Δ2C ; Shh Cre/+ embryos at E9.5 (Fig. 2U-W). As expected, this resulted in Ptch1 expression in adjacent nascent facial structures (Fig. 2P-R). Small, weak domains of Shh and Ptch1 expression were observed close to the midline, localized to the region of the optic stalk in Disp1 Δ2C/C829F ; ShhCre/+ embryos (not readily visible in Fig. 2T,Y). Only Disp1 Δ2/C829F; Shh +/-embr...

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Section: Introductionmentioning

confidence: 55%

Section: δ2/c829fmentioning

confidence: 99%

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Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand

Tian¹,

Jeong²,

Harfe

et al. 2005

Development

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“…By taking advantage of a hypomorphic mutant of Disp1, Shh signal in mice can be attenuated at several different levels. When Hh signal is decreased below certain degree, the maxillary incisors are missed [82]. The same tooth phenotype is also characterized in human holoprosencephaly (HPE) that results from reduced Shh signaling [83].…”

Section: Hhmentioning

confidence: 89%

Making a tooth: growth factors, transcription factors, and stem cells

et al. 2005

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Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions. These processes involve a series of inductive and permissive interactions that result in the determination, differentiation, and organization of odontogenic tissues. Multiple signaling molecules, including BMPs, FGFs, Shh, and Wnt proteins, have been implicated in mediating these tissue interactions. Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules. Adult stem cells are highly plastic and multipotent. These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation. Recent progress in the studies of molecular basis of tooth development, adult stem cell biology, and regeneration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.

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“…Shh), accumulation (e.g. Disp1) (Tian et al, 2004;2005;Etheridge et al, 2010) or transport (e.g. Cdo, Boc, Gas1) (Saha and Schaffer, 2006;Tenzen et al, 2006;Zhang et al, 2006;Allen et al, 2007;Seppala et al, 2007).…”

Section: Research Reportmentioning

confidence: 99%

Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape

et al. 2010

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SUMMARYVariation is an intrinsic feature of biological systems, yet developmental biology does not frequently address population-level phenomena. Sonic hedgehog (SHH) signaling activity in the vertebrate forebrain and face is thought to contribute to continuous variation in the morphology of the upper jaw, but despite its potential explanatory power, this idea has never been quantitatively assessed. Here, we test this hypothesis with an experimental design that is explicitly focused on the generation and measurement of variation in multivariate shape, tissue growth, cellular behavior and gene expression. We show that the majority of upper jaw shape variation can be explained by progressive changes in the spatial organization and mitotic activity of midfacial growth zones controlled by SHH signaling. In addition, nonlinearity between our treatment doses and phenotypic outcomes suggests that threshold effects in SHH signaling may play a role in variability in midfacial malformations such as holoprosencephaly (HPE). Together, these results provide novel insight into the generation of facial morphology, and demonstrate the value of quantifying variation for our understanding of development and disease.

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Dose dependency ofDisp1and genetic interaction betweenDisp1and other hedgehog signaling components in the mouse

Cited by 25 publications

References 61 publications

Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand

Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand

Making a tooth: growth factors, transcription factors, and stem cells

Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape

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