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RSK2 Is a Modulator of Craniofacial Development
BACKGROUND: 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 rar...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885557/ https://www.ncbi.nlm.nih.gov/pubmed/24416220 http://dx.doi.org/10.1371/journal.pone.0084343 |
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author | Laugel-Haushalter, Virginie Paschaki, Marie Marangoni, Pauline Pilgram, Coralie Langer, Arnaud Kuntz, Thibaut Demassue, Julie Morkmued, Supawich Choquet, Philippe Constantinesco, André Bornert, Fabien Schmittbuhl, Matthieu Pannetier, Solange Viriot, Laurent Hanauer, André Dollé, Pascal Bloch-Zupan, Agnès |
author_facet | Laugel-Haushalter, Virginie Paschaki, Marie Marangoni, Pauline Pilgram, Coralie Langer, Arnaud Kuntz, Thibaut Demassue, Julie Morkmued, Supawich Choquet, Philippe Constantinesco, André Bornert, Fabien Schmittbuhl, Matthieu Pannetier, Solange Viriot, Laurent Hanauer, André Dollé, Pascal Bloch-Zupan, Agnès |
author_sort | Laugel-Haushalter, Virginie |
collection | PubMed |
description | BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets. |
format | Online Article Text |
id | pubmed-3885557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38855572014-01-10 RSK2 Is a Modulator of Craniofacial Development Laugel-Haushalter, Virginie Paschaki, Marie Marangoni, Pauline Pilgram, Coralie Langer, Arnaud Kuntz, Thibaut Demassue, Julie Morkmued, Supawich Choquet, Philippe Constantinesco, André Bornert, Fabien Schmittbuhl, Matthieu Pannetier, Solange Viriot, Laurent Hanauer, André Dollé, Pascal Bloch-Zupan, Agnès PLoS One Research Article BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets. Public Library of Science 2014-01-08 /pmc/articles/PMC3885557/ /pubmed/24416220 http://dx.doi.org/10.1371/journal.pone.0084343 Text en © 2014 Laugel-Haushalter et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Laugel-Haushalter, Virginie Paschaki, Marie Marangoni, Pauline Pilgram, Coralie Langer, Arnaud Kuntz, Thibaut Demassue, Julie Morkmued, Supawich Choquet, Philippe Constantinesco, André Bornert, Fabien Schmittbuhl, Matthieu Pannetier, Solange Viriot, Laurent Hanauer, André Dollé, Pascal Bloch-Zupan, Agnès RSK2 Is a Modulator of Craniofacial Development |
title | 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_short | RSK2 Is a Modulator of Craniofacial Development |
title_sort | rsk2 is a modulator of craniofacial development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885557/ https://www.ncbi.nlm.nih.gov/pubmed/24416220 http://dx.doi.org/10.1371/journal.pone.0084343 |
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