The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Amanda J G Dickinson - One of the best experts on this subject based on the ideXlab platform.
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Using frogs faces to dissect the mechanisms underlying human orofacial defects.
Seminars in Cell & Developmental Biology, 2016Co-Authors: Amanda J G DickinsonAbstract:In this review I discuss how Xenopus laevis is an effective model to dissect the mechanisms underlying orofacial defects. This species has been particularly useful in studying the understudied structures of the developing face including the embryonic mouth and Primary Palate. The embryonic mouth is the first opening between the foregut and the environment and is critical for adult mouth development. The final step in embryonic mouth formation is the perforation of a thin layer of tissue covering the digestive tube called the buccopharyngeal membrane. When this tissue does not perforate in humans it can pose serious health risks for the fetus and child. The Primary Palate forms just dorsal to the embryonic mouth and in non-amniotes it functions as the roof of the adult mouth. Defects in the Primary Palate result in a median oral cleft that appears similar across the vertebrates. In humans, these median clefts are often severe and surgically difficult to repair. Xenopus has several qualities that make it advantageous for craniofacial research. The free living embryo has an easily accessible face and we have also developed several new tools to analyze the development of the region. Further, Xenopus is readily amenable to chemical screens allowing us to uncover novel gene-environment interactions during orofacial development, as well as to define underlying mechanisms governing such interactions. In conclusion, we are utilizing Xenopus in new and innovative ways to contribute to craniofacial research.
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Quantitative analysis of orofacial development and median clefts in Xenopus laevis.
Anatomical record (Hoboken N.J. : 2007), 2014Co-Authors: Allyson E. Kennedy, Amanda J G DickinsonAbstract:Xenopus has become a useful tool to study the molecular mechanisms underlying orofacial development. However, few quantitative analyses exist to describe the anatomy of this region. In this study we combine traditional facial measurements with geometric morphometrics to describe anatomical changes in the orofacial region during normal and abnormal development. Facial measurements and principal component (PC) analysis indicate that during early tadpole development the face expands primarily in the midface region accounting for the development of the upper jaw and Primary Palate. The mouth opening correspondingly becomes flatter and wider as it incorporates the jaw elements. A canonical variate analysis of orofacial and mouth opening shape emphasized that changes in the orofacial shape occur gradually. Orofacial anatomy was quantified after altered levels of retinoic acid using all-trans retinoic acid or an inhibitor of retinoic acid receptors or by injecting antisense oligos targeting RALDH2. Such perturbations resulted in major decreases in the width of the midface and the mouth opening illustrated in facial measurements and a PC analysis. The mouth opening shape also had a gap in the Primary Palate resulting in a median cleft in the mouth opening that was only illustrated quantitatively in the morphometric analysis. Finally, canonical and discriminant function analysis statistically distinguished the orofacial and mouth opening shape changes among the different modes used to alter retinoic acid signaling levels. By combining quantitative analyses with molecular studies of orofacial development we will be better equipped to understand the complex morphogenetic processes involved in Palate development and clefting. Anat Rec, 297:834–855, 2014. © 2014 Wiley Periodicals, Inc.
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Median facial clefts in Xenopus laevis: Roles of retinoic acid signaling and homeobox genes
Developmental biology, 2012Co-Authors: Allyson E. Kennedy, Amanda J G DickinsonAbstract:The upper lip and Primary Palate form an essential separation between the brain, nasal structures and the oral cavity. Surprisingly little is known about the development of these structures, despite the fact that abnormalities can result in various forms of orofacial clefts. We have uncovered that retinoic acid is a critical regulator of upper lip and Primary Palate development in Xenopus laevis. Retinoic acid synthesis enzyme, RALDH2, and retinoic acid receptor gamma (RARγ) are expressed in complementary and partially overlapping regions of the orofacial prominences that fate mapping revealed contribute to the upper lip and Primary Palate. Decreased RALDH2 and RARγ result in a median cleft in the upper lip and Primary Palate. To further understand how retinoic acid regulates upper lip and Palate morphogenesis we searched for genes downregulated in response to RARγ inhibition in orofacial tissue, and uncovered homeobox genes lhx8 and msx2. These genes are both expressed in overlapping domains with RARγ, and together their loss of function also results in a median cleft in the upper lip and Primary Palate. Inhibition of RARγ and decreased Lhx8/Msx2 function result in decreased cell proliferation and failure of dorsal anterior cartilages to form. These results suggest a model whereby retinoic acid signaling regulates Lhx8 and Msx2, which together direct the tissue growth and differentiation necessary for the upper lip and Primary Palate morphogenesis. This work has the potential to better understand the complex nature of the upper lip and Primary Palate development which will lead to important insights into the etiology of human orofacial clefts.
Johan Wikström - One of the best experts on this subject based on the ideXlab platform.
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Visualization of the fetal lip and Palate: is brain-targeted MRI reliable?
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association, 2013Co-Authors: Nuno Canto Moreira, Valentina Ribeiro, João F. Teixeira, Raili Raininko, Johan WikströmAbstract:Objective: To evaluate the ability of brain-targeted magnetic resonance imaging (MRI) to assess the anatomy of the fetal upper lip and Palate. Design: Two independent readers made a blind retrospective review of 60 brain-targeted MRIs of fetuses from 20 to 38 gestational weeks (GW). Fifty-five MRIs were normal and five had orofacial anomalies, including one isolated cleft lip and four cleft lip and Palate. Both normal and cleft MRIs had postnatal confirmation. The upper lip, Primary Palate, secondary Palate, and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis. Setting: Collaboration between a university hospital and a large private practice MRI center. Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the Primary Palate, 0.86 for the secondary Palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational ...
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Visualisation of the fetal lip and Palate: is brain-targeted MRI reliable?
Neurology, 2011Co-Authors: Nuno Canto Moreira, Valentina Ribeiro, Raili Raininko, João Paulo Teixeira, Johan WikströmAbstract:Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and Palate. Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up. Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft Primary Palates (two bilateral, two unilateral) and two cleft secondary Palates.The upper lip, Primary Palate, secondary Palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis. Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the Primary Palate, 0.86 for the secondary Palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and Primary Palates and in 93-97% of the normal secondary Palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft Palates. Conclusion: MRI in experienced hands seems reliable for assessment of the fetal lip and Palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and Palate in all fetal MRI examinations, since unsuspected clefts may be revealed.
Ralph S. Marcucio - One of the best experts on this subject based on the ideXlab platform.
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A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face
Development (Cambridge England), 2015Co-Authors: Nathan M. Young, Benedikt Hallgrimsson, Ralph S. MarcucioAbstract:The mechanisms of morphogenesis are not well understood, yet shaping structures during development is essential for establishing correct organismal form and function. Here, we examine mechanisms that help to shape the developing face during the crucial period of facial primordia fusion. This period of development is a time when the faces of amniote embryos exhibit the greatest degree of similarity, and it probably results from the necessity for fusion to occur to establish the Primary Palate. Our results show that hierarchical induction mechanisms, consisting of iterative signaling by Sonic hedgehog (SHH) followed by Bone morphogenetic proteins (BMPs), regulate a dynamic expression pattern of Shh in the ectoderm covering the frontonasal (FNP) and maxillary (MxP) processes. Furthermore, this Shh expression domain contributes to the morphogenetic processes that drive the directional growth of the globular process of the FNP toward the lateral nasal process and MxP, in part by regulating cell proliferation in the facial mesenchyme. The nature of the induction mechanism that we discovered suggests that the process of fusion of the facial primordia is intrinsically buffered against producing maladaptive morphologies, such as clefts of the Primary Palate, because there appears to be little opportunity for variation to occur during expansion of the Shh expression domain in the ectoderm of the facial primordia. Ultimately, these results might explain why this period of development constitutes a phylotypic stage of facial development among amniotes.
Nuno Canto Moreira - One of the best experts on this subject based on the ideXlab platform.
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Visualization of the fetal lip and Palate: is brain-targeted MRI reliable?
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association, 2013Co-Authors: Nuno Canto Moreira, Valentina Ribeiro, João F. Teixeira, Raili Raininko, Johan WikströmAbstract:Objective: To evaluate the ability of brain-targeted magnetic resonance imaging (MRI) to assess the anatomy of the fetal upper lip and Palate. Design: Two independent readers made a blind retrospective review of 60 brain-targeted MRIs of fetuses from 20 to 38 gestational weeks (GW). Fifty-five MRIs were normal and five had orofacial anomalies, including one isolated cleft lip and four cleft lip and Palate. Both normal and cleft MRIs had postnatal confirmation. The upper lip, Primary Palate, secondary Palate, and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis. Setting: Collaboration between a university hospital and a large private practice MRI center. Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the Primary Palate, 0.86 for the secondary Palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational ...
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Visualisation of the fetal lip and Palate: is brain-targeted MRI reliable?
Neurology, 2011Co-Authors: Nuno Canto Moreira, Valentina Ribeiro, Raili Raininko, João Paulo Teixeira, Johan WikströmAbstract:Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and Palate. Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up. Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft Primary Palates (two bilateral, two unilateral) and two cleft secondary Palates.The upper lip, Primary Palate, secondary Palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis. Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the Primary Palate, 0.86 for the secondary Palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and Primary Palates and in 93-97% of the normal secondary Palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft Palates. Conclusion: MRI in experienced hands seems reliable for assessment of the fetal lip and Palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and Palate in all fetal MRI examinations, since unsuspected clefts may be revealed.
Allyson E. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of orofacial development and median clefts in Xenopus laevis.
Anatomical record (Hoboken N.J. : 2007), 2014Co-Authors: Allyson E. Kennedy, Amanda J G DickinsonAbstract:Xenopus has become a useful tool to study the molecular mechanisms underlying orofacial development. However, few quantitative analyses exist to describe the anatomy of this region. In this study we combine traditional facial measurements with geometric morphometrics to describe anatomical changes in the orofacial region during normal and abnormal development. Facial measurements and principal component (PC) analysis indicate that during early tadpole development the face expands primarily in the midface region accounting for the development of the upper jaw and Primary Palate. The mouth opening correspondingly becomes flatter and wider as it incorporates the jaw elements. A canonical variate analysis of orofacial and mouth opening shape emphasized that changes in the orofacial shape occur gradually. Orofacial anatomy was quantified after altered levels of retinoic acid using all-trans retinoic acid or an inhibitor of retinoic acid receptors or by injecting antisense oligos targeting RALDH2. Such perturbations resulted in major decreases in the width of the midface and the mouth opening illustrated in facial measurements and a PC analysis. The mouth opening shape also had a gap in the Primary Palate resulting in a median cleft in the mouth opening that was only illustrated quantitatively in the morphometric analysis. Finally, canonical and discriminant function analysis statistically distinguished the orofacial and mouth opening shape changes among the different modes used to alter retinoic acid signaling levels. By combining quantitative analyses with molecular studies of orofacial development we will be better equipped to understand the complex morphogenetic processes involved in Palate development and clefting. Anat Rec, 297:834–855, 2014. © 2014 Wiley Periodicals, Inc.
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Median facial clefts in Xenopus laevis: Roles of retinoic acid signaling and homeobox genes
Developmental biology, 2012Co-Authors: Allyson E. Kennedy, Amanda J G DickinsonAbstract:The upper lip and Primary Palate form an essential separation between the brain, nasal structures and the oral cavity. Surprisingly little is known about the development of these structures, despite the fact that abnormalities can result in various forms of orofacial clefts. We have uncovered that retinoic acid is a critical regulator of upper lip and Primary Palate development in Xenopus laevis. Retinoic acid synthesis enzyme, RALDH2, and retinoic acid receptor gamma (RARγ) are expressed in complementary and partially overlapping regions of the orofacial prominences that fate mapping revealed contribute to the upper lip and Primary Palate. Decreased RALDH2 and RARγ result in a median cleft in the upper lip and Primary Palate. To further understand how retinoic acid regulates upper lip and Palate morphogenesis we searched for genes downregulated in response to RARγ inhibition in orofacial tissue, and uncovered homeobox genes lhx8 and msx2. These genes are both expressed in overlapping domains with RARγ, and together their loss of function also results in a median cleft in the upper lip and Primary Palate. Inhibition of RARγ and decreased Lhx8/Msx2 function result in decreased cell proliferation and failure of dorsal anterior cartilages to form. These results suggest a model whereby retinoic acid signaling regulates Lhx8 and Msx2, which together direct the tissue growth and differentiation necessary for the upper lip and Primary Palate morphogenesis. This work has the potential to better understand the complex nature of the upper lip and Primary Palate development which will lead to important insights into the etiology of human orofacial clefts.