RSK2 is a modulator of craniofacial development.
<h4>Background</h4>The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies enco...
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2014
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oai:doaj.org-article:59354c677b234ef4aa0e1bfbf8185d972021-11-18T08:38:35ZRSK2 is a modulator of craniofacial development.1932-620310.1371/journal.pone.0084343https://doaj.org/article/59354c677b234ef4aa0e1bfbf8185d972014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416220/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.<h4>Methodology/principal findings</h4>We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro.<h4>Conclusions</h4>This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets.Virginie Laugel-HaushalterMarie PaschakiPauline MarangoniCoralie PilgramArnaud LangerThibaut KuntzJulie DemassueSupawich MorkmuedPhilippe ChoquetAndré ConstantinescoFabien BornertMatthieu SchmittbuhlSolange PannetierLaurent ViriotAndré HanauerPascal DolléAgnès Bloch-ZupanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84343 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Virginie Laugel-Haushalter Marie Paschaki Pauline Marangoni Coralie Pilgram Arnaud Langer Thibaut Kuntz Julie Demassue Supawich Morkmued Philippe Choquet André Constantinesco Fabien Bornert Matthieu Schmittbuhl Solange Pannetier Laurent Viriot André Hanauer Pascal Dollé Agnès Bloch-Zupan RSK2 is a modulator of craniofacial development. |
| description |
<h4>Background</h4>The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.<h4>Methodology/principal findings</h4>We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro.<h4>Conclusions</h4>This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets. |
| format |
article |
| author |
Virginie Laugel-Haushalter Marie Paschaki Pauline Marangoni Coralie Pilgram Arnaud Langer Thibaut Kuntz Julie Demassue Supawich Morkmued Philippe Choquet André Constantinesco Fabien Bornert Matthieu Schmittbuhl Solange Pannetier Laurent Viriot André Hanauer Pascal Dollé Agnès Bloch-Zupan |
| author_facet |
Virginie Laugel-Haushalter Marie Paschaki Pauline Marangoni Coralie Pilgram Arnaud Langer Thibaut Kuntz Julie Demassue Supawich Morkmued Philippe Choquet André Constantinesco Fabien Bornert Matthieu Schmittbuhl Solange Pannetier Laurent Viriot André Hanauer Pascal Dollé Agnès Bloch-Zupan |
| author_sort |
Virginie Laugel-Haushalter |
| title |
RSK2 is a modulator of craniofacial development. |
| title_short |
RSK2 is a modulator of craniofacial development. |
| title_full |
RSK2 is a modulator of craniofacial development. |
| title_fullStr |
RSK2 is a modulator of craniofacial development. |
| title_full_unstemmed |
RSK2 is a modulator of craniofacial development. |
| title_sort |
rsk2 is a modulator of craniofacial development. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/59354c677b234ef4aa0e1bfbf8185d97 |
| work_keys_str_mv |
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