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AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome

Over the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma A...

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Autores principales: Laberthonnière, Camille, Novoa-del-Toro, Elva Maria, Chevalier, Raphaël, Broucqsault, Natacha, Rao, Vanitha Venkoba, Trani, Jean Philippe, Nguyen, Karine, Xue, Shifeng, Reversade, Bruno, Robin, Jérôme D., Baudot, Anais, Magdinier, Frédérique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301469/
https://www.ncbi.nlm.nih.gov/pubmed/34209568
http://dx.doi.org/10.3390/biomedicines9070751
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author Laberthonnière, Camille
Novoa-del-Toro, Elva Maria
Chevalier, Raphaël
Broucqsault, Natacha
Rao, Vanitha Venkoba
Trani, Jean Philippe
Nguyen, Karine
Xue, Shifeng
Reversade, Bruno
Robin, Jérôme D.
Baudot, Anais
Magdinier, Frédérique
author_facet Laberthonnière, Camille
Novoa-del-Toro, Elva Maria
Chevalier, Raphaël
Broucqsault, Natacha
Rao, Vanitha Venkoba
Trani, Jean Philippe
Nguyen, Karine
Xue, Shifeng
Reversade, Bruno
Robin, Jérôme D.
Baudot, Anais
Magdinier, Frédérique
author_sort Laberthonnière, Camille
collection PubMed
description Over the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma Arhinia and Microphthalmia Syndrome (BAMS), and the more recently isolated hypogonadotrophic hypogonadism (IHH) combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD). However, it remains unclear why certain mutations lead to a specific muscle defect in FSHD while other are associated with severe congenital anomalies. To gain further insights into the specificity of SMCHD1 variants and identify pathways associated with the BAMS phenotype and related neural crest defects, we derived induced pluripotent stem cells from patients carrying a mutation in this gene. We differentiated these cells in neural crest stem cells and analyzed their transcriptome by RNA-Seq. Besides classical differential expression analyses, we analyzed our data using MOGAMUN, an algorithm allowing the extraction of active modules by integrating differential expression data with biological networks. We found that in BAMS neural crest cells, all subnetworks that are associated with differentially expressed genes converge toward a predominant role for AKT signaling in the control of the cell proliferation–migration balance. Our findings provide further insights into the distinct mechanism by which defects in neural crest migration might contribute to the craniofacial anomalies in BAMS.
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spelling pubmed-83014692021-07-24 AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome Laberthonnière, Camille Novoa-del-Toro, Elva Maria Chevalier, Raphaël Broucqsault, Natacha Rao, Vanitha Venkoba Trani, Jean Philippe Nguyen, Karine Xue, Shifeng Reversade, Bruno Robin, Jérôme D. Baudot, Anais Magdinier, Frédérique Biomedicines Article Over the recent years, the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain Containing 1) chromatin-associated factor has triggered increasing interest after the identification of variants in three rare and unrelated diseases, type 2 Facio Scapulo Humeral Dystrophy (FSHD2), Bosma Arhinia and Microphthalmia Syndrome (BAMS), and the more recently isolated hypogonadotrophic hypogonadism (IHH) combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD). However, it remains unclear why certain mutations lead to a specific muscle defect in FSHD while other are associated with severe congenital anomalies. To gain further insights into the specificity of SMCHD1 variants and identify pathways associated with the BAMS phenotype and related neural crest defects, we derived induced pluripotent stem cells from patients carrying a mutation in this gene. We differentiated these cells in neural crest stem cells and analyzed their transcriptome by RNA-Seq. Besides classical differential expression analyses, we analyzed our data using MOGAMUN, an algorithm allowing the extraction of active modules by integrating differential expression data with biological networks. We found that in BAMS neural crest cells, all subnetworks that are associated with differentially expressed genes converge toward a predominant role for AKT signaling in the control of the cell proliferation–migration balance. Our findings provide further insights into the distinct mechanism by which defects in neural crest migration might contribute to the craniofacial anomalies in BAMS. MDPI 2021-06-29 /pmc/articles/PMC8301469/ /pubmed/34209568 http://dx.doi.org/10.3390/biomedicines9070751 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laberthonnière, Camille
Novoa-del-Toro, Elva Maria
Chevalier, Raphaël
Broucqsault, Natacha
Rao, Vanitha Venkoba
Trani, Jean Philippe
Nguyen, Karine
Xue, Shifeng
Reversade, Bruno
Robin, Jérôme D.
Baudot, Anais
Magdinier, Frédérique
AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title_full AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title_fullStr AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title_full_unstemmed AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title_short AKT Signaling Modifies the Balance between Cell Proliferation and Migration in Neural Crest Cells from Patients Affected with Bosma Arhinia and Microphthalmia Syndrome
title_sort akt signaling modifies the balance between cell proliferation and migration in neural crest cells from patients affected with bosma arhinia and microphthalmia syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301469/
https://www.ncbi.nlm.nih.gov/pubmed/34209568
http://dx.doi.org/10.3390/biomedicines9070751
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