Limits...
Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate.

Economou AD, Ohazama A, Porntaveetus T, Sharpe PT, Kondo S, Basson MA, Gritli-Linde A, Cobourne MT, Green JB - Nat. Genet. (2012)

Bottom Line: Furthermore, when a ruga was excised, new Shh expression appeared not at the cut edge but as bifurcating stripes branching from the neighboring stripe of Shh expression, diagnostic of a Turing-type reaction-diffusion mechanism.Genetic and inhibitor experiments identified fibroblast growth factor (FGF) and Shh as components of an activator-inhibitor pair in this system.These findings demonstrate a reaction-diffusion mechanism that is likely to be widely relevant in vertebrate development.

View Article: PubMed Central - PubMed

Affiliation: Department of Craniofacial Development, King's College London, UK.

ABSTRACT
We present direct evidence of an activator-inhibitor system in the generation of the regularly spaced transverse ridges of the palate. We show that new ridges, called rugae, that are marked by stripes of expression of Shh (encoding Sonic hedgehog), appear at two growth zones where the space between previously laid rugae increases. However, inter-rugal growth is not absolutely required: new stripes of Shh expression still appeared when growth was inhibited. Furthermore, when a ruga was excised, new Shh expression appeared not at the cut edge but as bifurcating stripes branching from the neighboring stripe of Shh expression, diagnostic of a Turing-type reaction-diffusion mechanism. Genetic and inhibitor experiments identified fibroblast growth factor (FGF) and Shh as components of an activator-inhibitor pair in this system. These findings demonstrate a reaction-diffusion mechanism that is likely to be widely relevant in vertebrate development.

Show MeSH

Related in: MedlinePlus

Sprouty and Shh loss-of-function mutants implicate FGF and Hedgehog signallng in rugal patterningPalates of P0 mice viewed from the oral side, anterior up. (a-d) Increased FGF signaling in Spry1−/−;Spry2−/− mutant mice results in disorganized and compacted rugae (b, detail in d) compared to wildtype (a, detail in c). Rugal phenotype can be distinguished despite cleft palate in these mutants. (e-h) Down-regulation of Shh in K14-Cre/Shhfl/fl mice results in a similar phenotype of disorganized, compacted rugae (f, detail in h) compared to wildtype controls (e, detail in g). Scale bar in panel a = 1 mm (for a, b, e, f); scale bar in panel c = 0.3 mm (for c, d, g, h).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3303118&req=5

Figure 3: Sprouty and Shh loss-of-function mutants implicate FGF and Hedgehog signallng in rugal patterningPalates of P0 mice viewed from the oral side, anterior up. (a-d) Increased FGF signaling in Spry1−/−;Spry2−/− mutant mice results in disorganized and compacted rugae (b, detail in d) compared to wildtype (a, detail in c). Rugal phenotype can be distinguished despite cleft palate in these mutants. (e-h) Down-regulation of Shh in K14-Cre/Shhfl/fl mice results in a similar phenotype of disorganized, compacted rugae (f, detail in h) compared to wildtype controls (e, detail in g). Scale bar in panel a = 1 mm (for a, b, e, f); scale bar in panel c = 0.3 mm (for c, d, g, h).

Mentions: Turing systems are defined by diffusible activator and inhibitor morphogens. Loss of Fgfr2 or Fgf10 genes results in a lack of palatal rugae 19,20 suggesting FGF as an activator in this system. To address this possibility, we examined mice lacking two intracellular antagonists of FGF signalling, Sprouty (Spry) 1 and Spry2 (i.e. compound mutant mice Spry1−/−;Spry2−/− (ref. 21)) as FGF signalling gain-of-function mutants. Spry1 and Spry2 are also FGF response markers and are expressed in palatal rugae during development (ref. 22, Supplementary Fig. S3 and data not shown). Spry1−/−;Spry2−/− mice showed highly disorganized palatal rugae including broader and ectopic ruga formation (Fig. 3a-d). Broader and disorganised rugae were prefigured by broader and disorganised Ptch1 expression associated with epithelial thickening at earlier stages (Supplementary Fig. S4). Palates from these mutants bore many tightly packed bumps rather than well-spaced ridges, suggesting more widespread as well as disorganised rugal tissue.


Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate.

Economou AD, Ohazama A, Porntaveetus T, Sharpe PT, Kondo S, Basson MA, Gritli-Linde A, Cobourne MT, Green JB - Nat. Genet. (2012)

Sprouty and Shh loss-of-function mutants implicate FGF and Hedgehog signallng in rugal patterningPalates of P0 mice viewed from the oral side, anterior up. (a-d) Increased FGF signaling in Spry1−/−;Spry2−/− mutant mice results in disorganized and compacted rugae (b, detail in d) compared to wildtype (a, detail in c). Rugal phenotype can be distinguished despite cleft palate in these mutants. (e-h) Down-regulation of Shh in K14-Cre/Shhfl/fl mice results in a similar phenotype of disorganized, compacted rugae (f, detail in h) compared to wildtype controls (e, detail in g). Scale bar in panel a = 1 mm (for a, b, e, f); scale bar in panel c = 0.3 mm (for c, d, g, h).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303118&req=5

Figure 3: Sprouty and Shh loss-of-function mutants implicate FGF and Hedgehog signallng in rugal patterningPalates of P0 mice viewed from the oral side, anterior up. (a-d) Increased FGF signaling in Spry1−/−;Spry2−/− mutant mice results in disorganized and compacted rugae (b, detail in d) compared to wildtype (a, detail in c). Rugal phenotype can be distinguished despite cleft palate in these mutants. (e-h) Down-regulation of Shh in K14-Cre/Shhfl/fl mice results in a similar phenotype of disorganized, compacted rugae (f, detail in h) compared to wildtype controls (e, detail in g). Scale bar in panel a = 1 mm (for a, b, e, f); scale bar in panel c = 0.3 mm (for c, d, g, h).
Mentions: Turing systems are defined by diffusible activator and inhibitor morphogens. Loss of Fgfr2 or Fgf10 genes results in a lack of palatal rugae 19,20 suggesting FGF as an activator in this system. To address this possibility, we examined mice lacking two intracellular antagonists of FGF signalling, Sprouty (Spry) 1 and Spry2 (i.e. compound mutant mice Spry1−/−;Spry2−/− (ref. 21)) as FGF signalling gain-of-function mutants. Spry1 and Spry2 are also FGF response markers and are expressed in palatal rugae during development (ref. 22, Supplementary Fig. S3 and data not shown). Spry1−/−;Spry2−/− mice showed highly disorganized palatal rugae including broader and ectopic ruga formation (Fig. 3a-d). Broader and disorganised rugae were prefigured by broader and disorganised Ptch1 expression associated with epithelial thickening at earlier stages (Supplementary Fig. S4). Palates from these mutants bore many tightly packed bumps rather than well-spaced ridges, suggesting more widespread as well as disorganised rugal tissue.

Bottom Line: Furthermore, when a ruga was excised, new Shh expression appeared not at the cut edge but as bifurcating stripes branching from the neighboring stripe of Shh expression, diagnostic of a Turing-type reaction-diffusion mechanism.Genetic and inhibitor experiments identified fibroblast growth factor (FGF) and Shh as components of an activator-inhibitor pair in this system.These findings demonstrate a reaction-diffusion mechanism that is likely to be widely relevant in vertebrate development.

View Article: PubMed Central - PubMed

Affiliation: Department of Craniofacial Development, King's College London, UK.

ABSTRACT
We present direct evidence of an activator-inhibitor system in the generation of the regularly spaced transverse ridges of the palate. We show that new ridges, called rugae, that are marked by stripes of expression of Shh (encoding Sonic hedgehog), appear at two growth zones where the space between previously laid rugae increases. However, inter-rugal growth is not absolutely required: new stripes of Shh expression still appeared when growth was inhibited. Furthermore, when a ruga was excised, new Shh expression appeared not at the cut edge but as bifurcating stripes branching from the neighboring stripe of Shh expression, diagnostic of a Turing-type reaction-diffusion mechanism. Genetic and inhibitor experiments identified fibroblast growth factor (FGF) and Shh as components of an activator-inhibitor pair in this system. These findings demonstrate a reaction-diffusion mechanism that is likely to be widely relevant in vertebrate development.

Show MeSH
Related in: MedlinePlus