Expression of Fgf signalling pathway related genes during palatal rugae development in the mouse

Porntaveetus, Thantrira; Oommen, Shelly; Sharpe, Paul T.; Ohazama, Atsushi

doi:10.1016/j.gep.2010.03.004

Cited by 20 publications

(24 citation statements)

References 41 publications

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“…Surprisingly, FGF signalling was in-phase with the Shh stripes in the mesenchyme but out-of-phase in the epithelium. This reconciles our previous description of FGF activity as being in phase with the Shh stripes (Economou et al, 2012) with a previous report describing it as out-of-phase (Porntaveetus et al, 2010). It also means that FGF signalling must be functioning as effectively two different pathways.…”

Section: Resultssupporting

confidence: 89%

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Perturbation analysis of a multi-morphogen Turing Reaction-Diffusion stripe patterning system reveals key regulatory interactions

Economou

Monk

Green

2019

Preprint

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Periodic patterning is extremely widespread in developmental biology and is broadly modelled by Reaction-Diffusion (RD) processes. However, the minimal two-component RD system is vastly simpler than the multimolecular events that current biology is now able to describe. Moreover, RD models are typically underconstrained such that it is often hard to meaningfully relate the model architecture to real interactions measured experimentally. To address both these issues, we investigated the periodic striped patterning of the rugae (transverse ridges) in the roof of the mammalian palate. We experimentally implicated a small number of major signalling pathways and established theoretical limits on the number of pathway network topologies that can account for the stable spatial phase relationships of their observed signalling outputs. We further conducted perturbation analysis both experimentally and in silico, critically to assess the effects of perturbations on established patterns. We arrived at a relatively highly-constrained number of possible networks and found that these share some common motifs. Finally, we examined the dynamics of pattern appearance and discovered a core network consisting of epithelium-specific FGF and Wnt as mutually antagonistic "activators" and Shh as the "inhibitor", which initiates the periodicity and whose existence constrains the network topology still further. Together these studies articulate the principles of multi-morphogen RD patterning and demonstrate the utility of perturbation analysis as a tool for constraining networks in this and, in principle, any RD system.

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Section: Resultssupporting

confidence: 89%

“…We were deliberately agnostic about the specific FGF ligand-receptor pair that was critical because multiple FGFs and FGF receptors are expressed in the palate (Porntaveetus, Oommen, Sharpe, & Ohazama, 2010). Both FGF and Shh are, by a number of experimental criteria, secreted, diffusible morphogens (Bokel & Brand, 2013;Dessaud et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Perturbation analysis of a multi-morphogen Turing Reaction-Diffusion stripe patterning system reveals key regulatory interactions

Economou

Monk

Green

2019

Preprint

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“…While our study does not confirm that the spatiotemporal change in Sox4 expression is due to cells migrating from the MEE to the rugae, it nevertheless is supported by evidence that palatal MEE cells are indeed migratory [54]. BMP7 and FGF signaling contribute to the formation of rugae [55,56], which serve as Shh signaling centers that mediate the extension of the palate in an anteroposterior direction [55,57]. Indeed, Fgf10 KO mice exhibit loss of rugae and CP [56].…”

Section: Discussionmentioning

confidence: 61%

“…BMP7 and FGF signaling contribute to the formation of rugae [55,56], which serve as Shh signaling centers that mediate the extension of the palate in an anteroposterior direction [55,57]. Indeed, Fgf10 KO mice exhibit loss of rugae and CP [56]. The anterior extension of the palate is driven by the temporal formation of rugae signaling centers that integrate Fgf10 and Bmp4 signaling to induce epithelial Shh expression [57].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Sox4 during Palate Development

et al. 2013

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Aim Identification of genes that contribute to secondary palate development provide a better understanding of the etiology of palatal clefts. Gene-expression profiling of the murine palate from gestational days 12–14 (GD12–14), a critical period in palate development, identified Sox4 as a differentially expressed gene. In this study, we have examined if the differential expression of Sox4 in the palate is due to changes in DNA methylation. Materials & methods In situ hybridization analysis was used to localize the expression of Sox4 in the developing murine secondary palate. CpG methylation profiling of a 1.8-kb upstream region of Sox4 in the secondary palate from GD12–14 and transfection analysis in murine embryonic maxillary mesenchymal cells using Sox4 deletion, mutant and in vitro methylated plasmid constructs were used to identify critical CpG residues regulating Sox4 expression in the palate. Results Spatiotemporal analysis revealed that Sox4 is expressed in the medial edge epithelium and presumptive rugae-forming regions of the palate from GD12 to GD13. Following palatal shelf fusion on GD14, Sox4 was expressed exclusively in the epithelia of the palatal rugae, structures that serve as signaling centers for the anteroposterior extension of the palate, and that are thought to serve as neural stem cell niches. Methylation of a 1.8-kb region upstream of Sox4, containing the putative promoter, completely eliminated promoter activity. CpG methylation profiling of the 1.8-kb region identified a CpG-poor region (DMR4) that exhibited significant differential methylation during palate development, consistent with changes in Sox4 mRNA expression. Changes in the methylation of DMR4 were attributed primarily to CpGs 83 and 85. Conclusion Our studies indicate that Sox4 is an epigenetically regulated gene that likely integrates multiple signaling systems for mediating palatal fusion, palatal extension and/or the maintenance of the neural stem cell niche in the rugae.

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“…A further six rugae are observed around the molar tooth areas, which have an oblique arrangement and which do not span the midline, as opposed to the anterior three rugae (Pantalacci et al 2008). Many nerve fibers that respond to touch and pressure on the palate are located in the palatal rugae (Ichikawa et al 2001;Kido et al 2003;Mitsui et al 2000;Nunzi et al 2004;Porntaveetus et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Shh signaling is essential for rugae morphogenesis in mice

Lee

Miyazawa

Shin

et al. 2011

Histochem Cell Biol

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Palatal ridges, or rugae palatinae, are corrugated structures observed in the hard palate region. They are found in most mammalian species, but their number and arrangement are species-specific. Nine palatal rugae are found in the mouse secondary palate. Previous studies have shown that epithelial Shh signaling in the palatal ridge plays an important role during rugae development. Moreover, Wnt family members, including LEF1, play a functional role in orofacial morphogenesis. To explore the function of Shh during rugae development, we utilized the maternal transfer of 5E1 (anti-Shh antibody) to mouse embryos. 5E1 induced abnormal rugae patterning characterized by a spotted shape of palatal ridge rather than a stripe. The expression patterns of Shh and Shh-related genes, Sostdc1, Lef1 and Ptch1, were disrupted following 5E1 injection. Moreover, rugae-specific cell proliferation and inter-rugae-specific apoptosis were affected by inhibition of Shh signaling. We hypothesize that the altered gene expression patterns and the change in molecular events caused by the inhibition of Shh signaling may have induced abnormal rugae patterning. Furthermore, we propose a reaction-diffusion model generated by Wnt, Shh and Sostdc1 signaling. In this study, we show that Sostdc1, a secreted inhibitor of the Wnt pathway, is a downstream target of Shh and hypothesize that the interaction of Wnt, Shh and Sostdc1 is a pivotal mechanism controlling the spatial patterning of palatal rugae.

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Expression of Fgf signalling pathway related genes during palatal rugae development in the mouse

Cited by 20 publications

References 41 publications

Perturbation analysis of a multi-morphogen Turing Reaction-Diffusion stripe patterning system reveals key regulatory interactions

Perturbation analysis of a multi-morphogen Turing Reaction-Diffusion stripe patterning system reveals key regulatory interactions

Epigenetic Regulation of Sox4 during Palate Development

Shh signaling is essential for rugae morphogenesis in mice

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