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

Biomedicines

Camille Laberthonnière¹  Anais Baudot¹  Jérôme D. Robin¹  Raphaël Chevalier¹  Karine Nguyen¹  Natacha Broucqsault¹  Jean Philippe Trani¹  Frédérique Magdinier¹  Elva Maria Novoa-del-Toro¹  Vanitha Venkoba Rao²  Shifeng Xue²  Bruno Reversade³ 

[1] Aix-Marseille Univ-INSERM, MMG, 13005 Marseille, France;Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore;Institute of Molecular and Cell Biology, A*STAR, Singapore 138632, Singapore;

关键词: SMCHD1;    Bosma Arhinia and Microphthalmia Syndrome;    Facio Scapulo Humeral Dystrophy;    RNA-Seq;    neural crest stem cells;    induced pluripotent stem cells;   

DOI  :  10.3390/biomedicines9070751

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown